The document provides an overview of the pharmaceutical industry and drug development process. It discusses how the industry is highly regulated and the various stages of drug development from target discovery through clinical trials and regulatory approval. It also outlines the major areas of pharmaceutical manufacturing including biochemical and chemical API production, bulk manufacturing, and packaging. Regulatory compliance and good manufacturing practices are essential throughout the manufacturing process.
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
This document gives detailed information regarding the processes followed in a Pharma Manufacturing Company.
It also includes graphical representation, for easy understanding.
Pharmaceutical Technology Transfer Best PracticesAnthony Grenier
Key Takeaways from the Technology Transfer Guidelines
• Standardize checklist for transferring product development, process development, and analytical method development knowledge
• Requirements are summarized in key deliverables and reports
Are you involved with planning tech transfer of your drug product? Join this webinar to learn more about the regulations and considerations you need to consider and learnings from a case study.
According to ICH Q10, “The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and ongoing continual improvement.”
As a result, there is an expectation for transfers to be performed in an organized, methodical manner with appropriate documentation. It is also expected that they happen between one Process Development group to another or to a Pilot Lab, from Process Development lab to clinical or commercial manufacturing, or from Process Development to external clinical manufacturing. Lastly, they may also happen between two company facilities at commercial scale, or between a company and an external contract manufacturing at commercial scale.
This presentation will cover points to consider for successful tech transfers with a focus on cGMP training requirements, and include lesson learned from real cases.
Presented by Guillaume Plane on September 22, 2016
In the last year or so the FDA and the EMA have issued new guidance/ draft guidance on "Process Validation".These align process validation activities with a product lifecycle concept and the International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System. The earlier guidelines were developed before the elaboration of the new ICH guidelines.With these new guidelines, additional opportunities are available to verify the control of the process by alternative means to the manufacture of traditional process validation batches. The main objective of process validation remains that a process design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9 and Q10 provide a structured way to define product critical quality attributes, design space, the manufacturing process and the control strategy. ICH Q8 refers to an ‘enhanced’ approach to pharmaceutical development which includes an alternative to the traditional process validation.
Continuous process verification [see definition in ICH Q8(R2) glossary] can be utilised in process validation protocols for the initial commercial production and for manufacturing process changes for the continual improvement throughout the remainder of the product lifecycle.
There is now a new paradigm in process validation. This presentation has been prepared from material available from FDA , EMA and ICH for beginners to have an overview of the new paradigm.
This document gives detailed information regarding the processes followed in a Pharma Manufacturing Company.
It also includes graphical representation, for easy understanding.
Pharmaceutical Technology Transfer Best PracticesAnthony Grenier
Key Takeaways from the Technology Transfer Guidelines
• Standardize checklist for transferring product development, process development, and analytical method development knowledge
• Requirements are summarized in key deliverables and reports
Are you involved with planning tech transfer of your drug product? Join this webinar to learn more about the regulations and considerations you need to consider and learnings from a case study.
According to ICH Q10, “The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and ongoing continual improvement.”
As a result, there is an expectation for transfers to be performed in an organized, methodical manner with appropriate documentation. It is also expected that they happen between one Process Development group to another or to a Pilot Lab, from Process Development lab to clinical or commercial manufacturing, or from Process Development to external clinical manufacturing. Lastly, they may also happen between two company facilities at commercial scale, or between a company and an external contract manufacturing at commercial scale.
This presentation will cover points to consider for successful tech transfers with a focus on cGMP training requirements, and include lesson learned from real cases.
Presented by Guillaume Plane on September 22, 2016
Pharmaceutical Industry Departments roles and responsibilities manasa life sc...ManasaLifeSciencesMa
Pharmaceutical Industry Departments and its roles and responsibilities were discussed. Product selection, Development, Manufacturing, Product approval, Marketing
InstantGMP Compliance Series - Facility DesignInstantGMP™
The design of facilities used in the manufacturing of dietary supplements must meet strict requirements for preventing mix-ups and cross contamination. This presentation describes how this can be done.
get to know how to manage your regulatory information better with Cunesoft. cune-RIM is designed by industry's request - easy to use, reliable, Cunesoft. The brand we trust!
https://cunesoft.com/en/products/rim/
[Note: This is a partial preview. To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
ISO 13485:2016 is an international standard that sets out the requirements for a quality management system (QMS) specific to the medical devices industry. The standard focuses on meeting customer and applicable regulatory requirements and is intended for any organization partially or fully involved in the medical device life-cycle.
This presentation can be used to brief your employees, new hires and potential auditees so as to create awareness of the ISO 13485:2016 standard. Alternatively, the presentation may be used to supplement your materials for the training of QA professionals and internal auditors in the medical devices industry.
It covers the what and why of ISO 13485, the QMS key clause structure, the audit approach and also offers practical tips on how to handle an audit session. When you are done teaching this material to your employees, they will be much more informed and comfortable with ISO 13485:2016.
LEARNING OBJECTIVES
1. Provide background knowledge on ISO 13485:2016
2. Gain an overview of ISO 13485:2016 structure and the certification process
3. Understand the audit approach
4. Gather useful tips on handling an audit session
CONTENTS
1. Overview of ISO 13485
About ISO
What are Standards?
Why are Standards Important?
What is ISO 13485?
Who is ISO 13485 For?
What is a Medical Device?
What is a Quality Management System?
How Does ISO 13485 Work?
Benefits that ISO 13485 Will Bring to the Organization
Advantages of Certification
Development of ISO 13485
Why Was ISO 13485 Revised?
Key Improvements to ISO 13485:2016
Relationship of ISO 13485 with ISO 9001
2. ISO 13485:2016 Structure
The ISO 13485:2016 Structure
The Plan-Do-Check-Act (PDCA) Process Model
ISO 13485:2016 Approach is Based on the PDCA Cycle
Documentation Requirements
ISO 13485:2016 Key Clause Structure (4-8)
Clause 4: Quality Management System
Clause 5: Management Responsibility
Clause 6: Resource Management
Clause 7: Product Realization
Clause 8: Measurement, Analysis & Improvement
3. ISO 13485:2016 Certification
Becoming ISO 13485:2016 Certified
ISO 13485:2016 Certification Process
4. Audit Approach
What is a Quality Audit?
What Are Audits Used For?
Types of Quality Audits
Internal Quality Audit
Principles of Auditing
Audit Focus
Audit Approach
Audit Emphasis
Document Review
Audit Findings
5. Handling an Audit Session
Rights of Auditee
Rights of Auditor
How to Handle an Audit Session?
Auditee's Conduct
Interacting with Auditors: Do's
Interacting with Auditors: Don'ts
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
This presentation covers the Introduction to Healthcare & different Products, Role of Pharmaceutical in Healthcare, Drug Details, What a drug is made of ?, Classification of drugs, Product Life Cycle of a Drug, Drug Development Phases, Regulatory Framework & various Regulatory Bodies
Pharmaceutical Industry Departments roles and responsibilities manasa life sc...ManasaLifeSciencesMa
Pharmaceutical Industry Departments and its roles and responsibilities were discussed. Product selection, Development, Manufacturing, Product approval, Marketing
InstantGMP Compliance Series - Facility DesignInstantGMP™
The design of facilities used in the manufacturing of dietary supplements must meet strict requirements for preventing mix-ups and cross contamination. This presentation describes how this can be done.
get to know how to manage your regulatory information better with Cunesoft. cune-RIM is designed by industry's request - easy to use, reliable, Cunesoft. The brand we trust!
https://cunesoft.com/en/products/rim/
[Note: This is a partial preview. To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
ISO 13485:2016 is an international standard that sets out the requirements for a quality management system (QMS) specific to the medical devices industry. The standard focuses on meeting customer and applicable regulatory requirements and is intended for any organization partially or fully involved in the medical device life-cycle.
This presentation can be used to brief your employees, new hires and potential auditees so as to create awareness of the ISO 13485:2016 standard. Alternatively, the presentation may be used to supplement your materials for the training of QA professionals and internal auditors in the medical devices industry.
It covers the what and why of ISO 13485, the QMS key clause structure, the audit approach and also offers practical tips on how to handle an audit session. When you are done teaching this material to your employees, they will be much more informed and comfortable with ISO 13485:2016.
LEARNING OBJECTIVES
1. Provide background knowledge on ISO 13485:2016
2. Gain an overview of ISO 13485:2016 structure and the certification process
3. Understand the audit approach
4. Gather useful tips on handling an audit session
CONTENTS
1. Overview of ISO 13485
About ISO
What are Standards?
Why are Standards Important?
What is ISO 13485?
Who is ISO 13485 For?
What is a Medical Device?
What is a Quality Management System?
How Does ISO 13485 Work?
Benefits that ISO 13485 Will Bring to the Organization
Advantages of Certification
Development of ISO 13485
Why Was ISO 13485 Revised?
Key Improvements to ISO 13485:2016
Relationship of ISO 13485 with ISO 9001
2. ISO 13485:2016 Structure
The ISO 13485:2016 Structure
The Plan-Do-Check-Act (PDCA) Process Model
ISO 13485:2016 Approach is Based on the PDCA Cycle
Documentation Requirements
ISO 13485:2016 Key Clause Structure (4-8)
Clause 4: Quality Management System
Clause 5: Management Responsibility
Clause 6: Resource Management
Clause 7: Product Realization
Clause 8: Measurement, Analysis & Improvement
3. ISO 13485:2016 Certification
Becoming ISO 13485:2016 Certified
ISO 13485:2016 Certification Process
4. Audit Approach
What is a Quality Audit?
What Are Audits Used For?
Types of Quality Audits
Internal Quality Audit
Principles of Auditing
Audit Focus
Audit Approach
Audit Emphasis
Document Review
Audit Findings
5. Handling an Audit Session
Rights of Auditee
Rights of Auditor
How to Handle an Audit Session?
Auditee's Conduct
Interacting with Auditors: Do's
Interacting with Auditors: Don'ts
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
This presentation covers the Introduction to Healthcare & different Products, Role of Pharmaceutical in Healthcare, Drug Details, What a drug is made of ?, Classification of drugs, Product Life Cycle of a Drug, Drug Development Phases, Regulatory Framework & various Regulatory Bodies
A descriptive research paper about the Foreign Direct Investment (FDI) in the Indian Pharmaceutical Industry.
It is a descriptive study on the history of FDI especially in the Indian Pharmaceutical Industry, as well as providing a SWOT Analysis, as well as information on the current market leaders and investors.
Also, the effect of government policies and recent financial changes are mentioned in the presentation
Active Pharma Ingredients (API) - Global Market Estimated to Reach US$ 21.9 b...Ajjay Kumar Gupta
Active Pharma Ingredients (API) - Global Market Estimated to Reach US$ 21.9 billion by 2023: Investment Opportunity for Startups and Entrepreneurs, Medications, Drugs and Pharmaceuticals, Cephalexin Monohydrate, Ampicilin Trihydrate, Ibuprofen Manufacturing Plant, Detailed Project Report, Profile, Business Plan, Industry Trends, Market Research, Survey, Manufacturing Process, Machinery, Raw Materials, Feasibility Study, Investment Opportunities, Cost and Revenue, Plant Economics, Production Schedule, Working Capital Requirement, Plant Layout, Process Flow Sheet, Cost of Project, Projected Balance Sheets, Profitability Ratios, Break Even Analysis
Production of active pharmaceutical ingredients is a highly sophisticated and technically demanding process. The global active pharmaceutical ingredient market is surging due to the increased demand for pharmaceutical drugs, which in turn is driven by aging population, increasing prevalence of chronic diseases such as cancer, diabetes, cardiovascular, neurological and infectious diseases among others. The global Active Pharmaceutical Ingredient market for was valued at US$ 12.9 bn in 2014 and is estimated to reach US$ 21.9 billion by 2023 at a CAGR of 6.3% from 2015 to 2023.
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The UK is at the forefront of the global pharmaceutical industry. As well as developing new medicines for many diseases, the pharmaceutical industry in the UK provides many other benefits to the British economy, including income, employment, expertise and major investment.
These slides offer a useful, referenced resource for members and visitors to our website who wish to share the story about the value of medicines. They complement existing resources available on the ABPI website and will be updated regularly as the ABPI updates other data and content.
It includes information about regulatory bodies, role of drug Regulatory professional, countries with their regulatory bodies, intellectual property rights, terminologies related to DRA, drug approval process, event regarding lack of Drug regulatory affairs
Welcome to our informative slide on the New Drug Application (NDA) - a pivotal milestone in the pharmaceutical world that propels medical innovation to new heights. In this concise presentation, we'll explore the significance of the NDA process and its critical role in bringing life-changing medications to patients in need.
Just to remind you that registrations for our 18th Pharmacovigilance 2019 event, which is taking place at The Pestana Chelsea Bridge Hotel in London, UK on 27-28th Feb are closing soon.For more details email to dinesh@virtueinsightsummits.com
2. ABOUT AUTHOR
The author of this document has extensive experience working on enterprise IT for
pharmaceutical industry.
This document draws heavily from the author’s experience, observations and reading.
Readers are invited to connect to the author on Linkedin by clicking on the below link:
The link is also on footer of all pages.
3. PHARMA CHALLENGES – IT CAN HELP
Pharma faces huge challenges.
IT can help.
To do that, IT teams need to understand pharma industry.
That is where this document comes in.
4. SCOPE
This document provides overview of pharmaceutical industry. It covers drug
development, manufacturing, distribution, sales, procurement, supply chains and
compliance. It also discusses several characteristics of pharmaceutical industry that set
it apart from other industries.
Since this is an overview document, advanced topics such as the below are out of
scope. Separate documents can be written if enough people are interested in these
topics:
Global pricing strategies of drugs
Challenges of patent cliffs and legal strategies to extend patent life
Impact of macroeconomic events such as Brexit on pharmaceutical industry
Recent legislation on drug safety in pharmaceutical supply chains and imperatives for IT
How technology such as big data analytics, RFID, IoT etc. can help pharma
And so on…
5. DISCLAIMER
This document is authored by an IT expert, not a drug production and distribution expert.
This document is for information of IT teams only. The author does not warrant that it is error-free and MAKES NO WARRANTIES, EXPRESS OR IMPLIED, OR OF
MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE, regardless of what is mentioned elsewhere in this document.
7. PURPOSE OF PHARMACEUTICAL INDUSTRY
The pharmaceutical industry discovers, develops, produces, and markets drugs or
pharmaceuticals for use as medications.
A drug is used to diagnose, cure, treat, or prevent disease.
8. HIGHLY REGULATED INDUSTRY
Pharma industry is highly regulated by regulatory agencies of governments
E.g.: FDA is regulatory agency in USA
Regulations are required to ensure safety and efficacy of drugs.
All drugs have to be approved by regulatory agencies.
Regulations also apply to all aspects that affect safety and efficacy of drugs
E.g.: production, procurement, quality control, distribution, IT systems, packaging,
tracking and tracing etc.
10. DRUG DEVELOPMENT: TARGET DISCOVERY
Identify target for drugs such as
• Proteins in human body
• Proteins in body of disease-causing microorganisms
Confirm role of the target in disease
11. DRUG DEVELOPMENT: DISCOVERY AND
DEVELOPMENT
Discovery:
• High throughput screening, computer based design to find molecular compounds that bind to target
• If the compound interacts with target in a way that may cure disease, it is called a ‘hit’
Development (Conduct experiments to understand):
• Absorption, distribution, metabolism and excretion of drug
• Benefits and mechanisms of action
• Best dosage and way to administer drug
• Toxicity
• Efficacy when compared to other drugs
• Interaction with other drugs
12. DRUG DEVELOPMENT: PRECLINICAL TRIALS
Preclinical trials in animals to determine
• Dosage
• Toxicity
• Whether it is safe to conduct clinical trials on human subjects
Treat animals ethically.
3Rs - Refine, Reduce and Replace animals where possible.
13. DRUG DEVELOPMENT: INVESTIGATIONAL NEW
DRUG PROCESS
Next stage is to conduct clinical trials on human subjects. But before that, the drug
developer/sponsor must obtain approval from regulator to go ahead.
Drug developer/sponsor submits an Investigational New Drug (IND) application to
regulators including below information:
• Animal study data and toxicity
• Clinical trial plans
• Information about investigator
IND submission will be reviewed by regulator.
If regulator is satisfied that there will be no unreasonable and significant risks to
human subjects in clinical trials, it will give approval to start clinical trials.
14. DRUG DEVELOPMENT: CLINICAL TRIALS
Clinical Trials – Phase 1
• 20 to 100 healthy human subjects
• Several months
• To collect safety and dosage information
Clinical Trials – Phase 2
Several hundred human subjects with disease
Several months to two years
To collect efficacy and side effects information
Clinical Trials – Phase 3
300 to 3000 human subjects with disease
1 to 4 years
To collect efficacy information and monitor adverse reactions information
15. DRUG DEVELOPMENT: GO TO MARKET
Company files application with regulator for approval to market drug
It is called NDA (New Drug Application). It includes
• Data from all trials - Preclinical to Clinical Trial Phase 3
• Studies, data, analysis, results
• Proposed labelling
• Safety updates
• Drug abuse information
• Directions for use etc.
Regulator gives approval to go to market if it is satisfied with safety and efficacy of the drug.
16. DRUG DEVELOPMENT: POST-MARKET SAFETY
MONITORING
True picture of a product’s safety actually evolves over time in market.
Regulator reviews reports of problems with drugs and
adds cautions to the dosage or usage information
Takes other measures for more serious issues
In some cases, regulator might require Clinical Trails Phase 4 to be conducted during the Post-
Market Safety Monitoring
18. PATENTS IN PHARMA
Patent:
A government authority or license conferring a right or title for a set period, especially
the sole right to exclude others from making, using, or selling an invention.
Please note:
Patent holder of a drug has exclusive right to manufacture and sell it
Patent is valid for a limited time
Patent validity time typically lasts 20 years from the date of filing
19. BRANDED DRUGS AND GENERICS
Branded drug: A drug that is marketed under brand name of the pharma company
that developed it
Generics
After patent expires even the companies that didn’t invent the drug are permitted to make and sell it.
These drugs are called generics
Generics are low cost
Branded drugs rapidly lose market once generics come to market
Some generics also use their own brand names
20. R&D AND PATENTS – IMPLICATIONS
R&D is risky, costly and time taking
• Out of 10,000 molecules that are ‘hits’ during drug discovery, only about 1 reaches market as drug
• It can take up to a couple of billions of US dollars to develop a drug
• It takes about 12 years to develop a drug
Implications of patents
Patent rights enable companies to charge high enough prices to recover high R&D costs
Patents are valid for a limited time - 20 years
Since R&D takes 12 years, effective life of patent is rendered much smaller
21. MAJOR PLAYERS IN PHARMA INDUSTRY
Large R&D based multinational companies
Large generic manufacturers
Local manufacturers in individual countries under
license or contract
Contract manufacturers
Drug discovery and biotechnology companies
Wholesalers
Retailers
Major retail chains
Hospitals
Online or mail order
23. WHAT MATERIALS GO INTO MAKING DRUGS
API Starting Material: Raw material, intermediate, or an API that is used in the production of an
API
API (Active Pharmaceutical Ingredient): Material that gives a drug its medicinal properties
Excipients: Inactive ingredients added to drug to give it properties such as: better taste, slow
dissolution, physical bulk etc.
Bulk: unpackaged drug such as tablets, capsules etc.
Packaging materials
Finished Packs: the labeled, packaged, final product
The terminology for these materials can be confusing. E.g.:
'API' is also called ‘Bulk Drug Substance'.
'Bulk' is also called ‘Formulated Drug Product'.
24. DRUG MANUFACTURING PROCESS - OVERVIEW
SECONDARY
MANUFACTURING
API
starting
materia
ls
Excipie
nts
Packa
ging
materi
als
Finished
Pack
PRIMARY
MANUFACTURING
PACKAGING
BulkAPI
25. DRUG MANUFACTURING PROCESS - OVERVIEW
API is a chemical that can be obtained by chemical or bio chemical synthesis
Bulk is obtained typically by mixing API with excipients and pressing the resulting
mixture into tablet form
Packaging is typically blister packaging of tablets. Packaging includes labelling and
may include repackaging
Processes of API manufacturing, bulk manufacturing and packaging are entirely
different. This is one of the reasons why they are typically carried out in separate
plants
Any part of manufacturing can be outsourced to contract organizations. Raw
materials or semi-finished goods at any stage of manufacturing can be purchased.
For example, no company manufactures all API it needs and procures the same from
outside vendors.
27. API MANUFACTURING: BIOCHEMICAL
Cells such as Bacteria, fungi or specific cells from mammals, plants or insects can
make chemicals.
These biologically obtained chemicals, or bio chemicals form API
Bio chemicals are produced by cells using the following mechanisms:
Bio chemicals produced by cells naturally
Bio chemicals produced by genetically modified cells
Bio chemicals in metabolic waste product of cells
28. BIOCHEMICAL API MANUFACTURING PROCESS
Fig: Biochemical API manufacturing process – biochemical synthesis
Cells multiply and produce bio chemicals during fermentation.
The bio chemicals are separated and purified during harvesting, recovery and purification.
FERMENTATION HARVESTING RECOVERY PURIFICATION
29. BIOCHEMICAL API: FERMENTATION IN BIO
REACTOR EXPLAINED
Fermentation of cells happens in equipment called bio reactor or fermenter
Bio reactor needs cells, nutritious growth medium for cells to multiply
Bio reactor may need additional ingredients to aid cell growth
Bio Reactor has
Ports for pumping/adding ingredients
Ports for drawing samples for process control
Sensors and meters for temperature, pressure etc.
Ports for Pumping out output product
30. BIOCHEMICAL API: FERMENTATION PROCESS
BIO REACTOR
PROCESS
- Mix ingredients
evenly
- Cells grow and
multiply
CELLS MULTIPLY IN
GROWTH MEDIUM IN
SHAKER FLASK
CELLS MULTIPLY IN
GROWTH MEDIUM IN
BIGGER CONTAINER
SET UP:
CLEANING AND SANITIZING EQUIPMENT
STERILIZING EQUIPMENT
PROCESS CONTROL SOFTWARE LOADED AND VERIFIED
CHECK ALL VALVES, CAPS, LINES
TIGHTEN HOSES AND CHECK FOR LEAKS
ADD
COMPONENTS TO
BIO REACTOR
- Pump cells from
container
- Pump growth
media
- Add stabilizers,
antibiotics,
antifoaming
agents etc.
BIO REACTOR
PROCESS
MONITORING
- Meters for
measuring
glucose, ph.,
pressure,
temperature
- Periodic
samples for
process control
OUTPUT OF FERMENTATION:
Broth is pumped into broth tank
31. BIOCHEMICAL API: SEPARATION/RECOVERY
EXPLAINED
Equipment used:
Centrifuge: It uses centrifugal action to separate mixture of solid and liquid
Homogenizer: this contains orifices smaller than cells. when cells pass through these orifices under high
pressure, body of cells are ruptured
Micro filter: filter very tiny remaining solids from liquid
Materials
Broth from fermentation contains cells which are solids and spent medium which is liquid
Bio chemical is contained in body of the cell in example process described here.
32. BIOCHEMICAL API: SEPARATION/RECOVERY:
PROCESS
SET UP:
Area cleaned and
disinfected
Equipment sanitized
Any updates to process
control software verified
BROTH TANK
BROUGHT TO
RECOVERY AREA.
BROTH PUMPED INTO
CENTRIFUGE
CENTRIFUGE
EXTRACTS CELL PASTE
WHICH IS SOLID AND
DISCARDS SPENT
MEDIUM WHICH IS
LIQUID
CELL PASTE IS
WASHED WITH
WATER. CENTRIFUGE
EXTRACTS CELL PASTE
FROM WATER
CELL IS DISRUPTED
USING
HOMOGENIZER
RESULT IS MIXTURE OF
SOLID CELL DEBRIS
AND LIQUID CELL
CONTENTS (LYSATE)
CENTRIFUGE
EXTRACTS LYSATE
REMAINING CELL
DEBRIS IS FILTERED
OUT USING MICRO
FILTER
RESULT IS CLARIFIED
LYSATE.
IT IS COLLECTED INTO A
TRANSFER VESSEL. THAT IS
TAKEN FOR FURTHER
PURIFICATION
33. BIOCHEMICAL API: PURIFICATION EXPLAINED
Column chromatography equipment, typically housed on mobile skid, has the
following:
Supply hose to feed clarified lysate to the column
Pre-filter to remove remaining particles
Column with beads for purification by
Size exclusion, ion-exchange chromatography, Hydrophobic interaction chromatography
Auto-switching valves for directing processed solution (waste/product)
Pumps to move clarified lysate through the process
Tangential flow filter with horizontal ultra-filtration membrane
Flow across the filter separates solution into permeate and retentate
34. BIOCHEMICAL API: PURIFICATION PROCESS
Set up
Clean, disinfect, organize
purification area.
Remove any unnecessary
equipment or materials
Clean, sanitize and setup
equipment as per SOP.
Gather materials
TRANSFER TANK
BROUGHT TO
PURIFICATION AREA.
CLARIFIED LYSATE
PUMPED INTO
CHROMATOGRAPHY
EQUIPMENT
CLARIFIED LYSATE
PASSES THROUGH
PREFILTER
PURIFICATION BY
COLUMN
CHROMATOGRAPHY.
(BUFFER SOLUTION
ADDED AS REQUIRED.)
RESULTING ELUATE
PUMPED INTO TFF
FILTER
MATERIALS ADDED TO
ELUATE TO AID
FILTERING – E.G.-
SALTS, BUFFER
SOLUTION ETC.
FINAL FILTRATION
RESULT IS BIOCHEMICAL
API.
API IS PACKED INTO
BOTTLES
OR
FREEZE DRIED AND PACKED
INTO BAGS
36. CHEMICAL API MANUFACTURING PROCESS
Fig: Chemical API manufacturing process – chemical synthesis
Series of chemical reactions are carried out on organic/inorganic chemicals
The result of reactions is purified using techniques such as extraction, filtration,
crystallization
The above diagram is highly simplified. The series of chemical reactions is typically a
multi-step process
CHEMICAL
REACTIONS
PURIFICATION
37. CHEMICAL API: CHEMICAL REACTIONS IN
REACTOR
Chemical reactions happen under controlled temperature and pressure in chemical
reactor
API starting materials such as reactants and catalysts required to make API, are input
to reactor.
Chemical reactor is reinforced pressure vessel with stainless steel, glass or metal
alloy linings
Chemical reactor has
Inlet valves
Outlet valves
Agitator for mixing
Sensors and meters
40. BULK MANUFACTURING: ALSO KNOWN AS
FORMULATION
Most common form of bulk is tablet. Others are syrup, injectable, orally disintegrating
strip etc.
Bulk is made using API and excipients.
Tablets are made by
Granulation of API and excipient mix.
Tableting
41. BULK: MANUFACTURING OF TABLETS
FIG: bulk: manufacturing of tablets
GRANULATION TABLETING COATING
42. BULK: MANUFACTURING OF TABLETS
The API and excipients must mix well into a powder
API and excipients mix must be granulized
Most common form of granulation is wet granulation
Tablet press compresses the granulized mix into tablets and ejects them
43. BULK: WET GRANULATION
The machine used to blend powders and add liquid is called granulator
The API and excipients weighed and blended together.
Liquid binding solution is added to blend while tumbling. This makes blended materials bind together
Then liquid is removed by drying the blend
Milling is done in Miller machine to enhance drying
Final blending is done in blender.
44. BULK: WET GRANULATION
Fig: Unit operations in granulation
PREBLENDING
LIQUID
BINDER
ADDITION
DRYING MILLING
FINAL
BLENDING
45. BULK: TABLETING
Tableting is performed in tablet press
Granules flow into molds that are in the shape of tablets
They are compressed into tablets and ejected from the tablet press
COMPRESSION EJECTION
46. BULK: COATING
FIG: COATING
Coating is performed in coating system.
LOAD TABLETS
TUMBLE TABLETS
IN WARM AIR
SPRAY COATING
COLLECT DUST
IN COLLECTION
BIN
48. PHARMACEUTICAL PACKAGING
Two types of packaging
Primary packaging
Secondary packaging
Characteristics of packaging
Protect tablets
Take care - Packaging materials should not react with tablets
Highly regulated - Mention approved usages, serial numbers, proper dosage, instructions, warnings,
expiry date etc.
50. PACKAGING: BLISTER PACKAGING
Blisters are formed on a sheet of forming web, using heat
Tablets are loaded into blisters
Lidding sheet is sealed on top
Blister packs are cut off
52. GMP: GOOD MANUFACTURING PRACTICES
Basically the government regulatory agency should be convinced that the
manufacturing process guarantees safety and efficacy of drugs.
A GMP is a system for ensuring that products are consistently produced and
controlled according to quality standards.
53. GMP: GOOD MANUFACTURING PRACTICES
GMP covers all aspects of production:
Starting materials
Premises and equipment
Training
Personal hygiene of staff
GMP works by:
Detailed, written procedures for each process that could affect the quality of the finished product.
Systems to provide documented proof that correct procedures are consistently followed
at each step in the manufacturing process
every time a product is made
55. PHARMACEUTICAL DISTRIBUTION: LOCATIONS
The locations between which goods physically flow are selected based on factors
such as proximity to end sales market, labor cost, taxation etc.
Domestic outsourcing, nearshoring or offshoring are possible.
A company may buy from its own subsidiary for optimizing taxes.
Generally financial flows and stock flows are maintained same.
56. PHARMACEUTICAL DISTRIBUTION: LOCATIONS
Most of world’s API sourced mostly from India and China
Packaging or repackaging is typically done in location near the end sales market
57. PHARMACEUTICAL DISTRIBUTION : LOCATIONS
Contract manufacturing is common in pharma. Contract Manufacturing Organizations
(CMOs) can make API or Bulk or Packaging or Repackaging for Big Pharma
companies
Contract manufacturing can be done by third parties in same country, nearshore or in
low cost locations such as China.
Total costs such as taxation, transportation, regulatory and supply risk and supply disruptions have to
be considered
Manufacturing locations of all contract manufacturers should be approved by
regulators
Likewise, all other vendors should be approved by regulators
Marketing authorization holder is responsible for any quality lapses of vendors
including contract manufacturers
58. PHARMACEUTICAL DISTRIBUTION : 3PL
Pharma companies may utilize services of 3PL for
Transporting
Freight Forwarding
Storing stock in 3PL owned DCs
Managing company’s own distribution centers
60. DRUG SAFETY IN SUPPLY CHAIN
Counterfeits can enter supply chain in following ways:
Adulteration
API or excipients Reduced, substituted or omitted
Drugs not manufactured as per GMP
Drugs manufactured at unapproved plants
Genuine products with altered labels
The problem is compounded with packaging and printing technologies that can make
packs and labels nearly identical to original.
61. DRUG SAFETY IN SUPPLY CHAIN
Motives for threats to integrity of supply chain:
Monetary gain – profit from selling counterfeits
Terrorism – use profits from selling counterfeits to fund terror activities
Theft – steal regulated drugs and divert them for substance abuse
62. DRUG SAFETY IN SUPPLY CHAIN
Some recent trends to ensure safe drug distribution:
Serialization
Authentication
Chain of custody software solutions
RFID tags: To identify genuine products and spot counterfeits
64. PHARMACEUTICAL SALES AND MARKETING
Pharma companies influence demand by
Detailing by pharma sales reps
Meaning promotion by sales reps in offices of doctors, and hospitals
Detailing is regulated
Managed care
Direct-To-Consumer campaigns
Advertising in medical journals
65. PHARMACEUTICAL SALES AND MARKETING
Pharmaceutical companies provide the below to healthcare providers
•Pharmaceutical marketing information
• Educate healthcare providers about new drugs, risks and benefits
• Reliable, valuable information
•Samples
• To help begin treatment sooner
• To help find right medicine
•Gifts to healthcare providers
• Care taken to ensure that gifts do not, and do not appear to, induce healthcare providers
• Legal requirements and ethical standards
66. PHARMACEUTICAL SALES AND MARKETING
Actions of payers also influence demand:
Examples of payers: insurance companies, Pharma Benefit Managers (PBMs)
Typical actions of payers that influence demand:
•Counterdetailing: Involves advising doctors of cheaper alternative
• Generics
• Therapeutic alternatives
•Sending letters to doctors
•Giving financial incentives to doctors to prescribe cheaper drugs
•Formulary design and utilization management
67. PHARMACEUTICAL SALES AND MARKETING
The below factors influence the drug prescribing decisions of doctors:
• Doctor’s knowledge and experience
• Patient’s unique situation
• Information from medical journals
• Inputs from colleagues and peers
• Patient’s financial situation
• Actions taken by pharma companies and payers, as discussed earlier
• and so on
68. PHARMACEUTICAL SALES AND MARKETING
Uncertainty of demands caused by:
Risk in pipeline drugs
Competition for patented drugs
Patent cliffs
Uncertainty in patent life extension strategies
Pricing pressures
69. PHARMACEUTICAL SALES AND MARKETING
Demand sensing challenges
Point of Sale data is not readily available
Purchased data from 3rd parties on filled prescription has a time lag of at least two weeks
70. PHARMACEUTICAL SALES AND MARKETING
Diversification of distribution channels increasing complexity of demand forecasting
Wholesalers, mail order, chain warehouses, stores, secondary wholesalers, specialty wholesalers,
hospitals and clinics – all providing demand data with varying degrees of completeness, timeliness and
accuracy
Consolidation of customer base decreasing complexity of demand forecasting
3 largest wholesalers account for 90% of US pharma distribution
72. FACTORS INFLUENCING PHARMA INDUSTRY
R&D challenges on the rise
Huge drug discovery costs
Really long lead time in drug discovery and development
Declining R&D productivity
Product lifecycle is long. However
Effective patent life is short
Competition-free patent life is even shorter
Onslaught of cheap generics
Therapeutic alternatives
73. FACTORS INFLUENCING PHARMA INDUSTRY
While regulation is really important to ensure drug safety and efficacy, it also throws
a host of challenges for pharma industry:
It slows down decision making
It introduces compliance risk into supply chains
Marketing Authorization Holder is responsible for noncompliance by suppliers
Getting dreaded warning letters from FDA seriously jeopardizes not only share prices, but also supply chains
Regulatory agencies have powers to close down entire plant if found non-compliant
It makes standardized operations, documentation and auditing really important
Innovation in manufacturing is fraught with regulatory risk and in many cases need regulatory
approval
It adds additional costs
74. FACTORS INFLUENCING PHARMA INDUSTRY
Flexibility is not easy
Because of audits, approvals, concerns about safety and efficacy of drugs, activities such as below are
slow and laborious:
Constructing new facility
Changing formulations
Inducting new vendors
Expanding to new geographies etc.
This affects agility and profitability of companies. For example, in case one raw material supplier does
not supply required materials, switching to new supplier is not easy
75. FACTORS INFLUENCING PHARMA INDUSTRY
Pharma companies growing by mergers and acquisitions
That influences demand, supply, economies of scale, opportunities for new synergies on the positive
side
It has associated complexities, risks and uncertainties on the negative side
76. FACTORS INFLUENCING PHARMA INDUSTRY
Pharmaceutical companies hold high inventory levels because:
R&D costs are huge compared to manufacturing costs
Patent period is limited to recover R&D costs
Need to maintain high customer service levels. Reasons being:
Steady supply essential for life saving drugs
Regulatory pressures to maintain steady supply
Penalties for supply disruptions
77. FACTORS INFLUENCING PHARMA INDUSTRY
Products have long lead times and limited shelf life
Temperature and humidity levels have to be carefully controlled during storage,
transportation etc.
Order filling accuracy has to be close to 100 percent. Especially expired drugs,
components or intermediate products should be timely identified, segregated and
discarded; not an easy task in huge warehouses
Warehouses should follow First Expiry First Out (FEFO) sequencing to improve
utilization of stocks
78. FACTORS INFLUENCING PHARMA INDUSTRY
API manufacturing has the following challenges
High cost
Long cycle times
API is manufactured in campaign manufacturing mode to:
Reduce set up costs
Reduce downtime costs
The challenges in API pose below risks pharma
Poor end to end responsiveness of pharma supply chains
Vulnerability to bullwhip effect
80. CONCLUSION
Pharma faces huge challenges.
IT can help.
To do that IT teams need to understand pharma industry.
That is where this document comes in.
