Good Engineering Practice (GEP) encompasses standards, guidelines, and methods for designing, constructing, and operating pharmaceutical and biotechnology facilities, while ensuring compliance, safety, and efficiency. Key components of GEP activities include project engineering, risk management, and cost management, alongside practices such as change management and continuous improvement. A comprehensive GEP approach can greatly enhance the overall operation and lifecycle management of pharmaceutical systems and processes.

1. GOOD ENGINEERING PRACTICE
BY: ADITYA SINGH
M. PHARM
1

2.  INTRODUCTION
• Good Engineering Practice (GEP) is defined as combination of standards,
specifications, codes, regulatory and industrial guidelines as well as
accepted engineering and design methods intended to design, construct,
operate, and maintain pharmaceutical and/or biotechnology facilities
taking into account not only regulatory compliance but also safety,
economics, environmental protection and operability. Standards and
specifications are provided by recognized sources such as established
engineering and architectural contractors as well as pharmaceutical
companies. Codes are provided by local, state, or federal jurisdictions
and/or insurance companies.
2

3. • GEP is one of the foundations on which other processes and systems are based
• E.g.: Equipment Qualification, Validation, GxP, GAMP, GMP and Quality Management
system.
• If implemented well – GEP will provide improvement in use of resources, cost, schedule,
quality, performance, safety, environment or other measurable factors that impact the
health of an organization.
GEP is one of the key concepts to ensure the introduction of equipment and systems
into facility meets user and regulatory requirements while being cost-effective,
compliant and well documented. 3

4. GEP activities include the following key concepts:
• Project Engineering
• Common Practices
• Operation and Maintenance
4

5. The three concepts at the core of most GEP activities
include:
• Risk Management
• Cost Management
• Organization and Control
5

6. 6

7. Common Practices, including
• Standards and Procedures
• Documentation Practices
• Change Management
• Innovation and Continuous Improvement
7

8. Operation and Maintenance, including
• Engineering Manuals and Records
• Breakdown Maintenance
• Internal Audit
• Equipment Decommissioning and Retirement
8

9.  ISPE GEP Guide:
• The ISPE Good Practice Guide covers the complete life cycle of engineering from
concept to retirement.
• The Guide:
• Aims to promote a common understanding of the concept and principles of GEP
defines and explains the term “Good Engineering Practice”
• Describes the fundamental elements existing in pharmaceutical and related
industries
9

10. • Identifies practices, demonstrating how GEP concepts may be applied
in the pharmaceutical industry considering the entire range of
pharmaceutical engineering activity
• Identifies key attributes of GEP, including how GEP relates and
interfaces with GxP
• The Guide divides GEP activity into three sections each prefaced with
the definition of the practice. Within each section, common practices
and sub-practices are identified to provide illustrative examples of
GEP.
10

11. • This enforcement policy addresses the Process Safety Management (PSM)
Standard's recognized and generally accepted good engineering practices
(RAGAGEP) requirements.
• The PSM Standard, 29 CFR 1910.119, directly references or implies the use of
RAGAGEP in three provisions:
• Employers must document that all equipment in PSM-covered processes
complies with RAGAGEP;
• Inspections and tests are performed on process equipment subject to the
standard's mechanical integrity requirements in accordance with RAGAGEP
 SOP IN GEP
11

12. • Inspection and test frequency follows manufacturer's recommendations and
good engineering practice, and more frequently if indicated by operating
experience.
• In addition, addresses situations where the design codes, standards, or
practices used in the design and construction of existing equipment are no
longer in general use. In such cases, the employer must determine and
document that the equipment is designed, maintained, inspected, tested, and
operating in a safe manner.
• As used in the PSM standard, RAGAGEP apply to process equipment design
and maintenance; inspection and test practices; and inspection and test
frequencies
12

13.  RISK MANGEMENT AS A PART OF GEP:
• To begin the risk management strategy, we need to define the risks that
could be involved with development, production, and distribution. Some
important questions to ask may be:
 What are the safety risks?
 Who is at risk?
 Are the risks predictable?
 Are they preventable?
13

14. • The industry widely uses two approaches to risk management:
• PROACTIVE: This approach identifies the threat exposure areas
to mitigate the potential for loss, before the loss occurs.
• REACTIVE: This approach investigates the threat exposure areas
to identify the root cause for loss and its control, after the loss
occurs.
14

15. 
AREA OF SCOPE FOR QUALITY RISK MANAGEMENT IN
THE INDUSTRY
• What is “Quality Risk Management”?
• Current global GMP regulations require that manufacturing processes
be designed and controlled to assure that in-process materials and the
finished product meet predetermined quality requirements and do so
consistently and reliably as demonstrated through Process Validation.
15

16. • Utilizing Quality Risk Management practices during the design and engineering
phase of a project is a regulatory expectation to manage risk associated with
product quality and patient safety. Risk management activities throughout a
system’s life cycle should be planned and documented for each system. Product
and process information (i.e., critical process parameters, critical quality
attributes, process control strategy information, and prior product / process
development and production experience, etc.) related to product quality and
patient safety should form the basis of science and risk-based decisions to
ensure that manufacturing systems are designed and verified as fit for the
system’s intended use. Unacceptable risks to product quality and patient safety
should be reduced to an acceptable level or eliminated, as much as possible,
prior to Process Validation.
16

17. • A well-written QRM procedure that describes the risk management
process requirements and step-by-step instructions is essential to
ensure that an organization can easily, repeatedly, and consistently
comply with QRM policy requirements and regulator expectations.
17

18. • The QRM process flow defined by ICH Q9, Quality Risk Management, is illustrated
below.
• There are a number of areas of opportunity that where the potential risk could be
managed, these include:
 Process
 Materials
 Facilities
 Manufacturing
 Distribution
 Patient
18

19.  RENOWNED METHODS FOR MANAGING OF RISKS IN THE
INDUSTRY:
• Qualitative: Qualitative analysis is the action of using subjective
information in determining a conclusion of a given unit without
proper statistical outcome. Qualitative analysis is used for
subjective decisions based on the non-quantifiable information,
generally it is used during root cause analysis to come up with
possible solutions.
19

20. • Quantitative: Quantitative analysis is structured statistical
analysis to estimate the risk how much involved in the
process/facility/system. Quantitative analysis is a statistical
analysis and is a combination of Severity, Probability and
Delectability.
• Risk Priority Number (RPN) can be established during quantitative
risk analysis and it is evolved by multiplication of identified values
of Severity (S), Probability (P), and Delectability (D).
20

21. • The RPN rating scale can be established in three levels i.e.
Low, Medium and High to estimate the identified risks are
at which level.
21

22. 22

23.  BASIC RISK MANAGEMENT TOOLS
• The Pharmaceutical industry and regulators can assess and manage the risks by
using recognized management tools.
• Below is the non-exhaustive list of some of the tools.
 Failure Mode Effects Analysis [FMEA]
 Failure Mode, Effects and Criticality Analysis [FMECA]
 Fault Tree Analysis [FTA]
 Hazard Analysis and Critical Control Points [HACCP]
 Hazard Operability Analysis [HAZOP]
 Preliminary Hazard Analysis [PHA]
23

24. • The final step in risk management is to develop a “mitigation”
strategy, to reduce risk even further. This should include
precautions such as:
 Backing up data
 Backup power generation
 Insurance
 Safety and emergency shutdown systems
24

25.  COST MANAGEMENT AS A PART OF GEP
• Cost management is a key aspect of good engineering practice
ensuring the cost impact of any activity understood, assessed
and managed in order to return good value. Value is measured
as a balance between cost, quality and progress
25

26. • In 2006, the pharmaceutical industry wasted $50 billion due to inefficient
manufacturing. Implementing and maintaining an efficient information
technology system saves time and money. These systems can help
report, track, and resolve deviations, track employees, and store data.
Utilizing IT adds a higher level of organization, which translates into a
higher level of production efficiency. Cutting these wasted dollars not
only makes the company more profitable, but more approachable to the
consumer
26

27.  PROJECT ENGINEERING AS A PART OF GEP
• It includes the following components:
 Project Infrastructure
 Project Organization
 Value Analysis
 Planning and Monitoring
 Design Reviews
 Handover
27

28. • Project engineering requires a lot of attention as well;
companies should have clearly defined procedures and
processes to follow. Implementing predefined tactics allows
for benchmarking and assessment, not only to run efficiently,
but to make any necessary changes that can improve
efficiency. Project engineering starts with organization
definition, which deploys the aforementioned tactics
28

29. • Defining procedures is also an essential component of GEP. Companies
who manufacture pharmaceuticals are more than likely to make more
than one product, so having a set of predetermined procedures for each
definition follows suit with consistency. Procedures should be defined
globally, and locally by process. This strategy should include process
structure, reporting structure, and a documentation structure.
29

30. • Some items that should have structured documentation are:
 Storage
 Planning
 Progress
 Cost
 Change
 Reviews
 Quality Control
30

31.  CHANGE MANAGEMENT IN GEP:
• The change management process in system
engineering is the process of requesting, determining
attainability, planning, implementing, and evaluating
of changes to a system. Its main goals are to support
the processing and traceability of changes to an
interconnected set of factors.
31

32.  DIRECTED CHANGES
• Directed changes are changes that are directed by the owner and are,
therefore, understood by the owner to be a change to the contract.
Subject always to the specific requirements of the contract,
• examples of directed changes include
• Addition or deletion of work
• Revision to material specifications
• Revision to project phasing
• Change to site access or hours of operation
• Change to contract duration
32

33.  CONSTRUCTIVE CHANGES
• Constructive changes typically result from the actions or inactions of the owner, and
usually are not intended or recognized by the owner to be a change. Subject to the
specific requirements of the contract, constructive changes might include Failure to
disclose material information (superior knowledge)
• Impossibility or impracticality of performing the work as designed (constructability)
• Imposition of joint occupancy or use of the project before completion
• Slow turnaround of submittals and requests for information
• Untimely inspections.
• Constructive changes are usually more difficult to recognize than directed changes
and, therefore, often become the basis for a dispute, or in the worst case, a formal
claim. 33

34.  CARDINAL CHANGES
• A cardinal change is a change that has the effect of making the work to be performed
• fundamentally different from the work the parties agreed to when the contract was
bid and awarded.
• An example of a cardinal change might be an owner’s instruction to remove asbestos
or other hazardous materials found on the project when the contract documents
identified no such materials and did not provide for their removal. Though this white
paper is not a legal treatise on the subject, a cardinal change is typically viewed as a
breach of contract by the owner and a contractor is not obligated to proceed with a
cardinal change if directed to do so by the owner.
34

35.  THE CHANGE MANAGEMENT PROCESS
• Construction contracts are unique in that they typically provide the owner the right
to make revisions to the contract documents without avoiding the contract.
Therefore, effectively managing changes requires successfully completing several
crucial activities that are described in this section. Again, although this process is not
exhaustive, it identifies the essential steps as follows:
 Step 1.Identify the contract requirements.
 Step 2.Identify the potential change and create a potential change order file.
 Step 3.Determine entitlement, measure the effect of the change, and calculate the
cost of the change.
 Step 4. Negotiate and execute the change order.
 Step 5.Maintain complete records of the executed change.
35

36.  REFERENCES
1. ISPE Good Engineering Practice Guide (accessed on Nov 6,
2017)
2. www.ispe.org ( accessed on Nov 6, 2017)
3. www.complianceteaminc.com ( accessed on Oct 25,2017)
4. www.ich.org (guideline 9 & 10) (accessed on Nov 10, 2017)
36