The document provides information on documentation practices in the pharmaceutical industry. It discusses why documentation is important, defining documentation as written evidence of activities. It states that regulatory bodies prioritize reviewing documents to verify activities. Good documentation practices, including systematic preparation and review of documents, are required to prevent errors and ensure compliance. Documentation provides records, traceability, and audit trails for investigation and review.

1. DOCUMENTATION IN
PHARMACEUTICAL
INDUSTRY
- Dr. Maitreyi N. Zaveri

2. GOLDEN RULE:
“ If it’s not documented, it didn’t
happen.”

3. What is a “DOCUMENT”?
• A DOCUMENT is a piece of written,
printed, or electronic matter that
provides information or evidence or that
serves as an official record.

4. Documentation ........ Why????
• Documents and products are produced in
pharmaceuticals but regulatory bodies are
interested to see documents first.
• Different documents can describe the
different activity in pharma and its actual
image.
• Due to the importance given to
documentation in pharma “good
documentation practices” is required.

5. Documentation ........ Why????
• Good documentation is a systematic
procedure of preparation, checking, verifying,
issuing, storing and reviewing of any
documents.
• Clearly written documents prevent errors of
various activities in Pharma.

6. Purpose of Documentation:
• Defines specifications and procedures for all
materials and methods of manufacture and
control.
• Ensures that all personnel knows what to do and
when to do it.
• Ensure that authorized persons have all
information necessary for release of product.
• Ensures documented evidence, traceability,
provide records and audit trail for investigation.
• Ensures availability of data for validation, review
and statistical analysis.

7. For good documentation the
organization should:
• Provide enough resources to create and complete
documentation.
• Ensure that the documents are attributable, legible, recorded,
original, and accurate,
• Conduct a thorough gap analysis of existing documentation
for any missing documentation or revision,
• Provide resources for initial and ongoing training to the
personnel, involved in development and manufacturing of the
pharmaceutical products, in documents creation,
management, and security of documents during lifecycle
management of products.
• Finally, an oversight of Quality Assurance is needed to ensure
that the personnel are following the organization SOPs.

8. What is drug substance??????
• Drug substance is an active ingredient that is
intended to furnish pharmacological activity
or other direct effect in the diagnosis, cure,
mitigation, treatment, or prevention of
disease or to affect the structure or any
function of the human body, but does not
include intermediates used in the synthesis of
such ingredient.

9. What is a drug product?????
• Drug product is a finished dosage form, e.g.,
tablet, capsule, or solution, that contains a
drug substance, generally, but not necessarily,
in association with one or more other
ingredients.
.

10. Exploratory
Product Development Brief (EPDB) for
Drug substance and Drug
product

11. Exploratory
Product Development Brief (EPDB)
• Many companies are finding themselves in an
environment that is uncertain, fast-changing and
increasingly complex.
• In this kind of environment, where much is unknown
and evolving, the traditional product development
approach cannot reliably identify new kinds of risk.
• It is not possible to completely define a product before
starting development.
• When companies try to maintain a traditional phased-
and-gated process in a changing environment, the
product development team is unable to manage to the
scope, timeline and budget approved at the outset.

12. Exploratory
Product Development Brief (EPDB)
• The result usually includes changing product
requirements, unexpected problems, rework,
schedule delays, breaking the budget and
commercial failure.
• The product development team needs an
approach that allows them to adapt to change
in customer needs, markets, competition,
technology and more.

13. Exploratory
Product Development Brief (EPDB)
• ExPD proposes a new approach to developing
products, using a two-pronged solution:
(1) treating product development from a
comprehensive systems perspective, and
(2) fundamentally redesigning the development
process based on reducing project uncertainties
and risk..

14. Exploratory
Product Development Brief (EPDB)
• ExPD differs from the traditional phased and gated
process in its fundamental redesign of the
development process to reduce uncertainties and
risks. It is an adaptive approach that responds
quickly to changes in internal and external factors.
• This process helps project teams identify, evaluate,
and prioritize uncertainties and risks throughout a
project. It then helps the team determine how and
when to resolve the uncertainty or when it is
appropriate to kill a project.

15. Product Development Plan (PDP)

16. What is Product Development Plan
(PDP)??????
• The overall process of strategy, organization,
concept generation, product and
marketing plan creation and evaluation, and
commercialization of a new product .
Innovative new products are the fuel for the
most powerful growth engine you can connect
to.

17. Key P’ceutical product development
milestones:

18. Pharmaceutical Development Report
Example QbD for Generic Drugs
Draft January 18, 2010
Product Development Report

19. Product Development Report
Table of Contents
1.1 Overview
1.2 Analysis of the Reference Product
1.3 Quality Target Product Profile (QTPP) for ANDA Product
2.1 Components of Drug Product
2.1.1 Drug Substance 16
2.1.1.1 Drug Substance Solubility
2.1.1.2 Drug Substance Polymorphism
2.1.1.3 Drug Substance Stability
2.1.1.4 Drug Substance Particle Size 2.1.2 Excipients 21
2.1.2.1 Excipient Compatibility Studies

20. 2.2 Drug Product
2.2.1 Formulation Development
2.2.1.1 Development PK Study 1001
2.2.1.2 Excipient Grade Selection
2.2.1.3 Formulation Risk Assessment
2.2.1.4 Formulation Study #1 Formulation Optimization
2.2.1.5 Formulation Study #2 Magnesium Stearate
2.2.2 Conclusions of Formulation Development 2.3 Process
Development
2.3.1 Identification of Critical Process Parameters
2.3.1.1 Pre-Granulation Blending
2.3.1.2 Roller Compaction and Milling
Product Development Report

21. 2.3.1.3 Granule Lubrication
2.3.1.4 Tablet Compression
2.3.2 Scale Up
2.3.3 Control Strategy
2.3.3.1 Control Strategy for Blending
2.3.3.2 Control Strategy for Roller Compaction and
Milling
2.3.3.3 Control Strategy for Lubrication
2.3.3.4 Control Strategy for Tablet Compression
2.3.3.5 Reduced Release Testing
3.1 Development Conclusions
Product Development Report

22. Master Formula Record

23. What is Master Formula Record?
• “A document or set of documents specifying
the starting materials with their quantities and
the packaging materials, together with a
description of the procedures and precautions
required to produce a specified quantity of a
finished product as well as the processing
instructions, including the in-process
controls.”

24. Master Formula Record
• There shall be Master Formula records
relating to all manufacturing procedures for
each product and batch size to be
manufactured. These shall be prepared and
endorsed by the competent technical staff i.e.
head of production and quality control.

25. The master Formula shall include: -
(a) the name of the product together with product
reference code relating to its specifications;
(b) the patent or proprietary name of the product along
with the generic name, adescription of the dosage form,
strength, composition of the product and batch size;

26. (c) a statement of the processing location and the principal
equipment to be used.
(d) name, quantity, and reference number of all the starting
materials to be used. Mention shall be made of any
substance that may .disappear. in the courts of processing.
(e) a statement of the expected final yield with the
acceptable limits, and of relevant intermediate yields,
where applicable.
The master Formula shall include: -

27.
(f) The methods, or reference to the methods, to be used
for preparing the critical equipments including cleaning,
assembling, calibrating, sterilizing.
(g) detailed stepwise processing instructions and the time
taken for each step;
(h) the instructions for in-process control with their limits;
The master Formula shall include: -

28. (i) the requirements for storage conditions of the products,
including the container, labelling and special storage
conditions where applicable;
(j) any special precautions to be observed; and
(k) packing details and specimen labels.
The master Formula shall include: -

29. Batch Manufacturing
Records

30. Batch Manufacturing Records.
• A batch manufacturing record is a document designed
to provide a complete record of the manufacturing
history of a batch of product. The terminology is
widely applied within the Pharmaceutical & Chemical
industries and is referenced in many of the
pharmaceutical and food regulatory agency
requirements.
• The US Food and Drug administration defines a batch
as “a specific quantity of a drug or other material that
is intended to have uniform character and quality,
within specified limits, and is produced according to a
single manufacturing order during the same cycle of
manufacture”.

31. • Batch Manufacturing Records are critical documents for
ensuring quality and regulatory requirements are achieved.
• They normally contain information that relates to the
following aspects of the manufacture of a batch of product:
– Dates of start and finish of manufacture.
– Lists all materials used and amounts of each used.
– Lists of packaging materials used.
– Details of the steps completed in the manufacturing
process and times of completion.
– Initials of the person responsible at every stage.
Batch Manufacturing Records.

32. –They normally contain information that relates to
the following aspects of the manufacture of a batch
of product: cont.....
–Details and results of all in-process checks.
–Reference to any equipment used.
–Batch yield and reconciliation.
–Any deviations.
–Quality Control information.
Batch Manufacturing Records.

33. • In many cases the Batch Manufacturing Records are written
in an instructional format with areas for the operator to fill in
processing information.
It is very important to provide the information in the Batch
Manufacturing Records where requested.
For certain critical operations, e.g. weighing of raw materials,
a second person must check calculations and identity of
materials and sign off on the Batch Manufacturing Records.
Batch Manufacturing Records.

34. • Each batch has an individual number, written on the Batch
Manufacturing Record.
• Batch Manufacturing Records must be:
Legible.
– Permanent.
– Accurate.
– Original.
– Signed.
• All corrections and deviations must be recorded and signed
off in the Batch Manufacturing Records.
Batch Manufacturing Records.

35. Batch Manufacturing Record.

36. Batch Reconciliation
• This is when quantities, e.g. of containers,
labels are checked against the worksheet at
critical points throughout the process.
Everything should be able to be accounted
for.

37. Batch Reconciliation
• % Reconciliation: Accounting of the material
used in the manufacturing and packaging.
• The formula is
• % Reconciliation
• Qty. Used + Qty. Returned + Samples + Others x 100
• Qty. Issued

38. Batch Packaging Records
• A Batch Packaging Record should be kept for each batch or
part batch processed. It should be based on the relevant parts
of the Packaging Instructions.
• The batch packaging record should contain the following
information:
• a) The name and batch number of the product,
• b) The date(s) and times of the packaging operations;
• c) Identification (initials) of the operator(s) who performed
each significant step of the process and, where appropriate,
the name of any person who checked these operations;

39. Batch Packaging Records
• d) Records of checks for identity and conformity with the
packaging instructions, including the results of in-process
controls;
• e) Details of the packaging operations carried out, including
references to equipment and the packaging lines used;
• f) Whenever possible, samples of printed packaging materials
used, including specimens of the batch coding, expiry dating
and any additional overprinting;
• g) Notes on any special problems or unusual events including
details, with signed authorisation for any deviation from the
Packaging Instructions;

40. Batch Packaging Records
• h) The quantities and reference number or identification of all
printed packaging materials and bulk product issued, used,
destroyed or returned to stock and the quantities of obtained
product, in order to provide for an adequate reconciliation.
• Where there are there are robust electronic controls in place
during packaging there may be justification for not including
this information.
• i) Approval by the person responsible for the packaging
operations

41. Print pack specifications
• The artwork must be checked by a competent
person, who is fully aware the labelling,
regulations, product details ,& the implications of
any mistake missed.
• The print colour should be chosen carefully.
• When dispensing the product, a label is usually
placed on the container or carton ,detailing the
dosage form & any other special instructions.
• Allowing a blank space on the pack for the
pharmacist’s label is worth considering when
designing the artwork.

42. Distribution Records
• Distribution records shall contain the name and strength of
the product and description of the dosage form, name and
address of the consignee, date and quality shipped, and lot
or control number of the drug product.
• For compressed medical gas products, distribution records
are not required to contain lot or control numbers.
• The primary purpose is to ensure that adequate data are
available to access trade customers should a recall be
initiated. The recording of lot number to each order will
certainly accomplish this purpose.

43. Distribution Records
• The recordings of dates on which a specific lot of product
commenced and ceased distribution may be used. All customers
receiving the product between these dates could then be
contacted.
• Obviously on the first and last days of distribution, some of the
customers may have received product from the end of previous lot
or the beginning of the next lot.
• This overlap should in no way adversely impact on the
effectiveness of a recall.
• Whatever system is used, it must accommodate the reintroduction
of returned goods into the distribution chain.

44. Distribution Records
• Distribution records include a wide range of documentation such as
invoices, bills of lading, customers’ receipts, internal warehouse
storage and inventory records.
• The information required need not be on every document. Also
customer codes and product codes may be used as alternates to
customer names and address and product names.

45. Certificate of Analysis (CoA)
• A document issued by a regulatory or quality
assurance entity verifying the adherence to
product specifications and standards of
production of certain products such as food
products and drugs. The certificate usually
includes the actual test results performed on
the product batch.

46. Site Master File
• The Site Master File is prepared by the pharmaceutical
manufacturer and should contain specific information
about the quality management policies and activities
of the site, the production and/or quality control of
pharmaceutical manufacturing operations carried out
at the named site and any closely integrated
operations at adjacent and nearby buildings.
• If only part of a pharmaceutical operation is carried
out on the site, a Site Master File need only describe
those operations, e.g. analysis, packaging, etc.

47. Drug Master File
• A Drug Master File (DMF) is a submission to
the Food and Drug Administration (FDA) that
may be used to provide confidential detailed
information about facilities, processes, or
articles used in the manufacturing, processing,
packaging, and storing of one or more
human drugs.