eclass73Certificate in eBioPharmaChem

Maria Kaluzna
Assignment 1 for the Foundation Module

14 Nov 2023, repeated

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You have covered a wide range of subjects in four primary categories throughout this brief foundation module. These subjects were selected for their applicability
to the production of safe and efficient medications and medical equipment.

The end-of-module assignment requires you to clearly demonstrate your knowledge and comprehension of the quality culture required to operate in a
manufacturing environment governed by GMP regulations. It also requires you to personally comprehend the rules that govern manufacturing, the guidelines for
applying those rules, and the risk management tools that help you make decisions based on science.

Select two themes from each of these four categories, as explained below, and compose a brief paragraph about each one.

Pick two topics from the “Quality Management Requirements for Good Manufacturing Practices (GMP)” list • Pick two topics from the “Process and Cleaning
Validation” list • Pick two topics from the “Quality Risk Management (QRM)” list • Pick two topics from the “Key Manufacturing Technologies” list

Guidelines: • Each of your answers should be approximately 200-words and therefore, your final assignment should be approximately a total of 1,500 words in
length. • It is highly recommended that you include diagrams where appropriate – so make sure to review your assignment before submitting it for where you can
include one. • Make sure to include a “reference list” or “bibliography” of anything you have used to help you answer the questions.

1. Quality Management Requirements for Good Manufacturing Practices (GMP) a) Describe the various ways drug products are administered. b) Give an overview
of the importance of patient safety and product quality for medicines and medical devices. c) List the key requirements of quality management system d) Describe
how to scientifically define product quality and the high-level principles of current good manufacturing practices (cGMP). e) Give an overview of the manufacturing’s
responsibilities for (a) designing, developing, and documenting product and processes, (b) examining inputs, (c) performing and monitoring operations, and (d)
addressing nonconformities.

2. Process and Cleaning Validation a) Define the terms - ‘validation’, ‘commissioning’, ‘qualification’ and ‘verification b) Give an overview of the specification, design,
and verification approach for equipment systems associated with the pharmaceutical, biopharmaceutical and medical device industries. c) Define installation
qualification (IQ), operational qualification (OQ) and performance qualification (PQ), and the typical project design documents are required to prepare such testing
protocols. d) Describe the cleaning validation sequence and the basis for quantification limits and how to determine cleanliness levels on the basis of the analytical
testing of representative samples.

3. Quality Risk Management (QRM) a) Describe the importance of risk management and the basic steps involved in its application b) Give an overview of the risk
management tool ‘Fault Tree Analysis’ and where and how we can use it. c) Detail the main steps in performing a ‘Failure Mode, Effects Analysis’ (FMEA) and the
important modes of (a) failure, (b) factors causing these failures, and (c) the likely effects of these failures. d) Describe the management of a complete risk
management process in terms of identify risk, analyzing risk, evaluating risk and controlling risk.

4. Key Manufacturing Technologies a) Detail the typical equipment and process stages of the manufacture of active pharmaceutical ingredients (API) using batch
organic chemistry synthesis b) Describe the biopharmaceutical manufacturing process and its 3-stage process sequences, i.e. Upstream Processing; Fermentation
/ Bio-reaction; Downstream Processing c) Give an overview of the critical process parameters and quality attributes associated with the manufacture of medicinal
tablets. d) Give an overview of the critical process parameters and quality attributes associated with aseptic processing and terminal sterilization products for
parenteral products. e) Describe the generation, storage and distribution pharmacopeia grade purified water (PUW). f) Describe the storage and distribution of
pharmacopeia grade water for injection (WFI) g) Give an overview of the common cleanroom configuration and airflow direction, filter arrangements, cleanroom
garments, and personnel and material flows h) Detail the personnel and material flows in a controlled airflow environment designed to contain high potency
chemicals.

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1. Quality Management Requirements for Good Manufacturing Practices (GMP)

b) Give an overview of the importance of patient safety and product quality for medicines and medical devices.

Patient Safety and Product Quality (and Data Integrity)

Product Q

Identity, Effectiveness/Efficacy, Safety/Purity, Potency, Strength.

https://learning.getreskilled.com/pluginfile.php/2267788/mod_resource/content/3/1-
6%20Focus%20on%20Patient%20Safety%20and%20Product%20Quality.pdf

Fitness for Intended Use

The overall performance, fitness for intended purpose can be ensured through Performance Qualification or Verification, which focus on critical-to-quality
attributes. In summary, this will establish that the equipment or system is functioning adequately for its intended use, the associated process is well-regulated,
and the potential hazards, risks to the patient have been successfully mitigated, hence fulfilling the validation criteria set by regulatory authorities. Several
pharmaceutical businesses engage in intricate, time-consuming, costly qualification practices. Certain parts of certification can enhance the suitability of
equipment and systems for their intended use, purpose, whereas other aspects frequently lack this value, do not add this value. The prescriptive and inflexible
rules and procedures around qualification, as often performed, might diminish its total worth, overall value. GMP regulations establish the foundation for the
actions known as qualification, but they do not specify the precise practices, specific requirements that should be followed during qualification.

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Ways to Build Patient Safety + Security into Medical Device Innovations

https://www.linkedin.com/pulse/achieving-patient-safety-security-medical-device-ama-frimpong/

/177 words count without links and sources/

Resources:

1. Brown Taylor, Greenlight Guru, Understanding the Quality Control Process in Medical Device Manufacturing, J a n u a r y 9 , 2 0 2 2 ,
https://www.greenlight.guru/blog/quality-control-
process#:~:text=Quality%20assurance%20prevents%20flaws%20in,might%20result%20in%20nonconforming
%20products.
2. eBioPharmaChem certificate GetReskilled materials, 1-6 Focus on Patient Safety and Product Quality,
https://learning.getreskilled.com/pluginfile.php/2267788/mod_resource/content/3/1-
6%20Focus%20on%20Patient%20Safety%20and%20Product%20Quality.pdf.

3. Frimpong Ama, —IET Young Woman Engineer of the Year 2022 || Top 50 Women in Engineering 2022, Achieving Patient Safety and Security in
Medical Device Development, May 7, 2023, https://www.linkedin.com/pulse/achieving-patient-safety-security-medical-device-ama-frimpong/.
4. IFPMA, Quality, safety, and efficacy of therapeutical products, 2023, https://www.ifpma.org/areas-of-work/strengthening-regulatory-systems/quality-
safety-and-efficacy-of-therapeutical-products/.

5. Johnson & Johnson, Position on Patient Safety, https://www.jnj.com/about-jnj/policies-and-positions/our-position-on-patient-safety.

e) Give an overview of the manufacturing’s responsibilities for (a) designing, developing, and documenting product and processes, (b) examining inputs, (c)
performing and monitoring operations, and (d) addressing nonconformities.

https://www.biopharminternational.com/view/monitoring-biopharmaceutical-processes-present-and-future-approaches

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https://www.nqa.com/en-us/resources/blog/November-2018/corrective-
actions#:~:text=Assemble%20a%20team%20of%20people,it%20as%20completely%20as%20possible.

Design, Develop, Document Product + Processes

In a manufacturing environment, product features should be specified from design to delivery, and control over modifications is maintained. Establishing,
authorizing, controlling quality, production processes is crucial, along with documenting processes for variability.

Resources, facilities, Procedures (process); Identification of process owner; Identification +control of variables; Quality control measures, data collection,
monitoring, controls (product + process); Validation activities, operating ranges, acceptance criteria; Effects on related process, functions, or personnel.

The quality system model requires managers to ensure technical specialists set product requirements + process parameters, understanding pharmaceutical
science, equipment, facilities, and process types. It doesn't directly address packaging and labeling reg. (FDA 211 Subpart G).

Examine Inputs

In a modern quality systems framework, input refers to any substance in a finished product, including materials like chemicals, process water, gas, containers,
closures. An effective system ensures reliability by implementing quality controls for receipt, manufacture, storage, utilization. CGMP laws mandate testing,
preliminary tests, regular supplier audits. Procedures cover acceptance, use, rejection, disposal of facility-generated items.

Perform, Monitor Operations

A quality systems approach is crucial for manufacturers to verify, validate, and monitor activities, ensuring scientifically sound controls, establishing requirements,
documenting process parameters. Modern equipment and continuous monitoring expand knowledge, and experience improves process understanding.

Quality systems manage nonconformities, deviations, documenting investigation, conclusion, follow-up. They measure process. product qualities to ensure
product compliance with needs and expectations. Proper documentation, handling -are crucial, discrepancy investigation methods are essential. Products or
processes not meeting criteria must be segregated.

/244 words without links and books/

Sources:

1. eBioPharmaChem certificate GetReskilled materials, Pharmaceutical Facility Design Section 4-8 Quality Systems Approach – Manufacturing,
https://learning.getreskilled.com/pluginfile.php/2267815/mod_resource/content/3/4-8%20Quality%20Systems%20Approach%20-
%20Manufacturing.pdf.

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 2. FDA, Guidance for Industry, Pharmaceutical CGMPs, September 2006, https://www.fda.gov/media/71023/download.

3. NQA, ADDRESSING NON-CONFORMANCES AND CORRECTIVE ACTIONS, 07 November 2018, https://www.nqa.com/en-us/resources/blog/November-

2018/corrective-actions#:~:text=Assemble%20a%20team%20of%20people,it%20as%20completely%20as%20possible.
4. Rathore Anurag S., Monitoring of Biopharmaceutical Processes: Present and Future Approaches, BioPharm International, BioPharm International-05-
01-2009, Volume 22, Issue 5, Pages: 40–45, May 1, 2009, https://www.biopharminternational.com/view/monitoring-biopharmaceutical-processes-
present-and-future-approaches.

5. Speer Jon, Greenlight Guru, The Art of Defining Design Inputs and Design Outputs, J a n u a r y 8, 2020,
https://www.greenlight.guru/blog/defining -design-inputs-and-design-outputs.
6. Zhang Xiang, Cresswell Mark, Science Direct, Future Development of iCRT in Inorganic Controlled Release Technology, 2016,
https://www.sciencedirect.com/topics/materials-science/design-control.

1 Process and Cleaning Validation

a) Define the terms - ‘validation’, ‘commissioning’, ‘qualification’ and ‘verification.

In the pharmaceutical manufacturing industry, commissioning, qualification, validation are three processes that are critical to ensuring that equipment, facilities,
and systems make safe, effective medicines.

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Traditional Qualification Process (adapted from the typical V-Model)

OPQ Validation Process (fromV-M)

Food manufacturing professionals and engineers use terms like qualifications, validations, verifications, and commissioning interchangeably, but there's no
standard. FDA regulations mandate Process Validation programs, and accepted methods include consensus guides and industry guidance.

Verification

The term "validation" refers to the demonstration of a method's suitability for its intended purpose, while "verification" is the demonstration that the method is
suitable for specific experimental conditions. The literature often confuses the terms "system suitability tests" and "validation" interchangeably, as the primary
objective is to ensure the verified procedure functions effectively in the intended circumstances. It is crucial to differentiate between these terms to avoid
confusion.

https://www.pharmtech.com/view/qualification-validation-and-verification

Chromatographic systems offer resolution and repeatability, similar to validation processes. Nonsterile items should not hinder microbial development. Process
verification studies ensure efficient commercial processes.

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https://www.ema.europa.eu/en/documents/presentation/presentation-general-concepts-process-validation-kowid-ho_en.pdf

https://www.perfval.com

Photo by Trnava University on Unsplash

https://www.spai-srl.com/pq-performance-qualification-and-the-difference-with-process-
validation/?lang=en#:~:text=In%20other%20cases%2C%20the%20PQ,be%20used%20to%20make%20up

/164 words and a chart is a picture- dyscalculia now…, neither links nor sources included/

Sources:

1. ASTM International. (2013). E2500-13: Standard guide for specification, design, and verification of pharmaceutical and biopharmaceutical
manufacturing systems and equipment. West Conshohocken, PA: ASTM International.
2. Blackburn Timothy D., PE, A Practical Approach to Commissioning and Qualification - A Symbiotic Relationship, July-Aug 2004pdf,
https://ispe.org/sites/default/files/attachments/public/July-Aug-2004.pdf.
3. Creaner Gerry, B.Chem Eng and Fitzgerald Donagh, B.Prod Eng GetReskilled, Glossary of Pharmaceutical Validation Terms, Jan 2022,
https://www.getreskilled.com/validation/validation-
glossary/#:~:text=Validation%20%E2%80%93%20creating%20a%20documented%20evidence,a%20consistent%20and%20reproducible%20result.
4. Evenbound - Jeralin, Angstrom Technology, WHAT DO THE GMP QUALIFICATION & VALIDATION PROCESSES LOOK LIKE?, Cleanroom Standards, Jun
27, 2022, https://angstromtechnology.com/what-do-the-gmp-qualification-validation-processes-look-
like/#:~:text=GMP%20qualification%20is%20the%20act,and%20comply%20with%20specified%20requirements.
5. FDA (1987). "Guidelines on General Principles of Process Validation".
6. FDA (1983). "Guide to Inspection of Computerised Systems (The Blue Book)". US Food and Drug Administration, Maryland, USA.
7. Fitzgerald Donagh, B.Prod Eng, and Wilson claire, BSc, GetReskilled, Commissioning vs Qualification vs Validation in the Pharmaceutical Manufacturing
Industry, March 2023, https://www.getreskilled.com/validation/qualification-validation/#claire

8. Ho Kowid, EMA Europe, ANSM, Workshop on process validation General concepts on process validation,
https://www.ema.europa.eu/en/documents/presentation/presentation-general-concepts-process-validation-kowid-ho_en.pdf.
9. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use [ICH]. (2005). Quality risk
management. Retrieved from https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf.
10. Lyons Jesseca, Greenlight Guru, IQ, OQ, PQ: A Quick Guide to Process Validation, J a n u a r y 20, 2023,
https://www.greenlight.guru/blog/iq-oq-pq-process-validation.
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 11. PharmTech, Advanced Development and Manufacturing, Qualification, Validation, and Verification, Pharmaceutical Technology, Pharmaceutical
Technology-04-02-2007, Volume 31, Issue 4, April 2, 2007, https://www.pharmtech.com/view/qualification-validation-and-verification.
12. Performance Validation Blog, Commissioning and Qualification – An Overview, 2022-2023, https://www.perfval.com/commissioning-and-qualification-
an-overview/#:~:text=Commissioning%20is%20a%20systematic%20approach,%5BISPE%7D%2C%202007).
13. Precision Solutions, IQ OQ PQ for Pharmaceutical, https://www.precisionsolutionsinc.com/iq-oq-pq-for-pharmaceutical/.
14. Wikipedia Encyclopaedia, Validation (drug manufacture), last edited on 3 September 2023,
https://en.wikipedia.org/wiki/Validation_(drug_manufacture), Process performance qualification protocol, last edited on 18 October 2021,
https://en.wikipedia.org/wiki/Process_performance_qualification_protocol.

c) Define installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ), and the typical project design documents are required
to prepare such testing protocols.

https://www.arenasolutions.com/resources/glossary/installation-qualification/

Installation qualification (IQ) is a crucial process for ensuring the correct delivery, installation, and configuration of critical equipment, piping, software, or
instruments. It involves verifying technical specifications, comparing contents to packing lists, confirming installation, verifying connections, supplementary
instruments, energy provision, calibration dates.

https://learning.getreskilled.com/pluginfile.php/2267844/mod_resource/content/2/8-1%20-%20PQ%20-%20OQ%20-%20IQ.pdf

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V-Model for “Direct Impact” Systems

Calibration is a crucial qualification program in Direct Impact systems, documented through an IQ protocol, which aids in qualifying processes and eliminates
repetition.

Operational qualification is a crucial stage in quality assurance, involving independent testing of equipment components to ensure they function according to
manufacturer's specifications. It involves collaboration between C&Q engineers, maintenance workers, process, chemical, automation, instrumentation, and
mechanical engineers. OQ is FDA-regulated and ensures the functionality of facilities, utilities, or equipment affecting product quality. Commissioning integration
with OQ can be achieved through capacity testing, examination of alarms, interlocks, sequencing, FAT.

Performance qualification (PQ) is a crucial process in the manufacturing industry, involving comprehensive testing to ensure equipment and systems are suitable
for their intended use. It includes data summary, manufacturing conditions, calibration, validation, sampling plan, analysis methodology, variability limits, and
nonconformance contingencies, regulated by the FDA.

-- Validation Master Plan (VMP);

- User Requirements Brief, Requirement Spec.;

- Supplier’s Drawings, Specifications:

• Purchase Orders, Contracts;

• Manufacturer's Data Sheets;

• Process Description;

• Piping, Instrumentation Diagrams P&IDs;

• Equipment;

• System Hardware / Software Spec.;

• Instrument.

- Functional Requirement Spec.;

- Equipment operations manuals;

-SOPs;

• Alarm/Interlock;

• Control system operation manuals;

• References for local, national, international codes, standards.

- Relevant regulations, standards, specifications provided by the owner,

- The PQ document specify the system approval requirements.

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• HVAC Systems: Zoning Diagrams, (area, room pressurizations).

• Acceptance requirements for standard grades of water, such as Water for Injection (WFI) + Purified Water, Pharmacopoeia+.

• Purify Compressed Gases.

+Doc. for implementation.

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 /SOP/Compilation [email protected]

/282 words – no links, no ref. count/

References:

1. Andersson Sofia, ELOS Medtech, IQ, OQ, PQ: What do they mean? And why are they important in medical device manufacturing?, March 30, 2021,
https://elosmedtech.com/iq-oq-pq-what-do-they-mean-and-why-are-they-important-in-medical-device-manufacturing/.

2. Arena, Glossary, What is Installation Qualification IQ?, https://www.arenasolutions.com/resources/glossary/installation-qualification/.

3. Creaner Gerry, B.Chem Eng. and Fitzgerald Donagh, B.Prod Eng, GetReskilled, What are IQ OQ PQ and why are they critical to making safe medicines in
the Pharmaceutical Industry?, July 2023, https://www.getreskilled.com/what-are-iq-oq-pq/.

4. Digital Life Sciences, PQ (Performance Qualification), https://www.digital-ls.de/en/glossar/pq-performance-qualification/.

5. eBioPharmaChem certificate GetReskilled materials, 8-1 - PQ - OQ – IQ,

https://learning.getreskilled.com/pluginfile.php/2267844/mod_resource/content/2/8-1%20-%20PQ%20-%20OQ%20-%20IQ.pdf.
6. Engyte, A Guide to IQ, OQ, and PQ in FDA-Regulated Industries, https://www.egnyte.com/guides/life-sciences/oq.

7. The FDA Group, A Basic Guide to IQ, OQ, PQ in FDA-Regulated Industries, 19 MAY 2022, HTTPS://WWW.THEFDAGROUP.COM/BLOG/A-BA.
8. ISPE Baseline Guide Volume-5 “Commissioning and Qualification”. (2001).

9. Ofni systems, Installation Qualification, https://www.ofnisystems.com/services/validation/installation-

qualification/#:~:text=A%3A%20The%20FDA%20definition%20of,manufacturer%20recommendations%20are%20suitably%20considered.

3. Quality Risk Management (QRM)

c) Detail the main steps in performing a ‘Failure Mode, Effects Analysis’ (FMEA) and the important modes of (a) failure, (b) factors causing these failures, and (c)
the likely effects of these failures.

FMEA, or probable failure modes and effects analysis, is a method developed by the US military in the 1940s to identify potential problems in design, manufacturing,
assembly processes, products, or services. It focuses on identifying failures based on severity, frequency, and detection ease, with the goal of eliminating or reducing
critical ones and chronicling current knowledge for continuous development. FMEA is primarily used in the pharmaceutical industry for identifying failures and
dangers related to production processes.

FMEA can be expanded to assess consequences' severity, probability, and detectability, resulting in a FMECA. Risk = probability of failure x severity category. FMEA
can be applied to equipment and facilities, analyzing manufacturing operations and their effect on a product or process. It identifies elements/operations within
the system that render it vulnerable.

FMEACs include potential failure modes, such as process, people, equipment, materials, methods, facilities/environment, and measurements. The steps in
performing a FMEAC include an analysis team, goal, ground rules, information, defining system, activity, potential failure modes, effects, rate effect for impact,
probability, detection, calculate RPN, prioritize actions, select controls, prepare a report, and retain data.

FMEA/FMEAC to identify causes, effects of generic failures in computer applications used in regulatory environments. Hazards include physical/environmental
issues, such as loss of system integrity, software failure, inability to meet testing commitments, as well as human-related issues like operator errors, inaccurate
SOPs, incorrect access rights. These consequences can range from data integrity loss to business inefficiencies.
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https://asq.org/quality-resources/fmea

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https://learning.getreskilled.com/pluginfile.php/2267904/mod_resource/content/6/3-4%20-%20FMEA.pdf

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Books and references:

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 1. American Society for Quality, What is FMEA? Failure Mode & Effects Analysis, https://asq.org › quality-resources › fmea
2. eBioPharmaChem certificate GetReskilled materials, 3-4 - Failure Mode, Effects (and Criticality) Analysis (FMEA / FMEAC),
https://learning.getreskilled.com/pluginfile.php/2267904/mod_resource/content/6/3-4%20-%20FMEA.pdf
3. Juran, Guid e to Fa ilu re Mode an d Effect Ana lys is – FMEA, April 2, 2018, https://www.juran.com/blog/guide-to-failure-mode-and-effect-
analysis-fmea/.
4. Safety Culture, FMEA: Definition, Steps, Types, & Tools, 21 Apr 2023, https://safetyculture.com/topics/fmea/.
5. Wikipedia Encyclopaedia, Failure mode and effects analysis.

Failure Mode and Effect Analysis: An ASQ Pocket Guide.

FMEA from Theory to Execution: Failure Mode And Effect Analysis.
Investigation Handbook and Effective CAPA Systems.
Risk Management Using Failure Mode And Effect Analysis in the Quality Toolbox.

d) Describe the management of a complete risk management process in terms of identify risk, analyzing risk, evaluating risk and controlling risk.

Organizes hazards that could compromise safety, quality, reliability, durability of a product, process, program, evaluates + plans effective actions.

Risk assessment involves identifying hazards, evaluating their associated risks. Quality assessments start with a clear problem description, considering
potential issues, failure probability, repercussions to identify the right risk management tool.

Risk identification involves systematic use of historical data, theoretical analysis, stakeholder perspectives to identify hazards in a problem, inquiry. It
forms the basis for quality risk management, assessing risk level, probability of harm.

Risk analysis aims to understand the nature of risks by considering uncertainties, sources, events, likelihood, consequences, effectiveness of current,
potential future controls, with accuracy enhanced by high-quality, accurate information.

Risk evaluation is the comparison of recognised, analysed risks with predetermined risk criteria. Risk evaluations involve assessing the robustness of
evidence pertaining to the three core inquiries.

Risk assessment quality relies on robust data collection, assumptions, and credible uncertainty sources, including pharmaceutical science knowledge
gaps, potential damage, problem discovery likelihood.

Risk control involves making decisions to mitigate, acknowledge hazards, with goal of reducing risk to an acceptable level. The effort should be
proportional to the risk's magnitude; decision makers can use methodologies like benefit-cost analysis.

Risk communication between decision-makers + stakeholders.

https://glceurope.com/blog/quality-risk-management-qrm-in-pharmaceutical-industry

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 548 × 576

https://www.azonano.com/article.aspx?ArticleID=6283#:~:text=It%20is%20a%20quantitative%20or,over%20their%20occurrence%20and%20detection.

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/200 words count, no figures, no links, no references/

References:

1. C a m m s G r o u p , Managing Risk in the Pharmaceutical & Life Sciences Sector, https://cammsgroup.com/blog/managing-risk-in-the-pharmaceutical-

sector/#:~:text=Most%20pharmaceutical%20%26%20Life%20Sciences%20companies,quality%20data%2C%20and%20siloed%20systems.
2. e B i o P h r m a C h e m c e r t i f i c a t e G e t R e s k i l l e d m a t e r i a l s , 8-2 - Documenting the QRM Process, Module 1 pdf.
3. EMA/CHMP/ICH/24235/2006 +ICHQ9.

4. E u r o p e a n M e d i c i n e s A g e n c y , ICH guideline Q9 on quality risk management, EMA/CHMP/ICH/24235/2006 Committee for Human Medicinal
Products, September 2015.
5. FDA, Risk Evaluation and Mitigation Strategies | REMS, https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-
rems#:~:text=A%20Risk%20Evaluation%20and%20Mitigation,the%20medication%20outweigh%20its%20risks.

6. Fujitsu, Risk Management for the Pharmaceutical Industry, https://www.fujitsu.com/downloads/SVC/fc/article/pharma-risk-mgmt.pdf.

7. GLC Europe, Quality Risk Management (QRM) in Pharmaceutical Industry, https://glceurope.com/blog/quality-risk-management-qrm-in-pharmaceutical-
industry.
8. N I C H O L S E T I E N N E , Greenlight Guru, ISO 14971 Risk Management for Medical Devices: The Definitive Guide, https://www.greenlight.guru/blog/iso-
14971-risk-management, M a y 1 1 , 2 0 2 3 .
9. P a l m e r P a u l , Understanding Risk Management in the Pharmaceutical Industry, May 1, 2023, https://www.linkedin.com/pulse/understanding-risk-
management-pharmaceutical-industry-paul-palmer/.

4. Key Manufacturing Technologies

d) Give an overview of the critical process parameters and quality attributes associated with aseptic processing and terminal sterilization products for parenteral
products.

Requirements in a cGMP environment for formulating, filtering, filling parenteral drugs + combination devices. It emphasizes the importance of aseptic processing,
bioburden in protecting sterile products, patients. Filtering is designed to screen out microbes, particles (Amazon filters UK). Challenges include wetting, plugging,
filter failure, integrity test suppression.

https://biomanufacturing.org/uploads/files/632590861923645435-bioman-2015-kruszynski-parenteral-filling.pdf

The term parenteral is usually used for drugs given by injection or infusion. A Critical Process Parameter (CPP) -term used in pharmaceutical production for process
variables which have an impact on a critical quality attribute (CQA) and, therefore, should be monitored or controlled to ensure the drug product obtains the
desired quality. At-line process analysers or in-line/on-line process sensors are frequently used to monitor physical + chemical CPPs.

Bacterial endotoxins, product sterility, particulate matter are also considered to be CQAs for injectable pharmaceutical products. CQAs are generally ensured
through a good pharmaceutical quality system, by implementing an effective control strategy.

Pharmaceutical manufacturers use aseptic processing or terminal sterilization to produce safe, effective products free of pathogens and contaminants. Terminal
sterilization is preferred by regulatory agencies for simple solutions or small molecules, as it controls bioburden accumulation. Aseptic processing sterilizes
manufacturing and packaging components before filling and assembling the drug product, creating a sterile envelope. Sterile Finished Pharmaceuticals are final
products free from living organisms or contaminants, requiring aseptic conditions for preparation. Terminal sterilisation is preferred, while aseptic processing
maintains a sterile environment. HVAC systems use HEPA filters for purified air. Industry cleanliness levels are categorized as "classes" or "grades".

Terminal sterilization reduces workload, costs by tracing back to pure products until absolute sterility is achieved during recrystallization. Small-molecule
parenteral medicines, particularly heart drugs, require sterilization due to their importance in hospitals.

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Sterile Finished Pharmaceuticals are final products free from living organisms or contaminants, requiring aseptic conditions for preparation.

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https://www.altasciences.com/sites/default/files/2021-12/The-Altascientist_issue-21_Terminal-Sterilization.pdf

/276 words, no links, no ref./

Bibliography:

1. The Altascientist (scientific journal), issue no 21, Terminal sterilization, https://www.altasciences.com/sites/default/files/2021-12/The-

Altascientist_issue-21_Terminal-Sterilization.pdf

2. Adlerz Katrina, Biomanufacturing, Quality & Regulatory, RoosterBio, Critical Quality Attributes (CQAs): Know Their Importance & Limitations in Product &
Process Development, April,27,2021.

3. Biomanufacturing.org, PRIMARY MANUFACTURING PARENTERAL FORMULATION, FILTERING, AND FILLING,

https://biomanufacturing.org/uploads/files/632590861923645435-bioman-2015-kruszynski-parenteral-filling.pdf

4. eBioPharmaChem certificate GetReskilled materials, 7-6 - Sterile Manufacturing,

https://learning.getreskilled.com/pluginfile.php/2267965/mod_resource/content/4/7-6%20-%20Sterile%20Manufacturing.pdf

5. Hamilton, What are Critical Process Parameters (CPPs)?, https://www.hamiltoncompany.com/process-analytics/process-analytical-technology/critical-

process-parameters#:~:text=A%20Critical%20Process%20Parameter%20(CPP,product%20obtains%20the%20desired%20quality.
6. Mendicino M, Bailey AM, Wonnacott K, Puri RK, Bauer SR. MSC-based product characterization for clinical trials: an FDA perspective. Cell Stem Cell.
2014;14(2):141-5; doi: 10.1016/j.stem.2014.01.013.
7. Administration FaD. Guidance for industry: Potency tests for cellular and gene therapy products. Center for Drug Evaluation and Research (CDER). 2011;
doi: https://bit.ly/3q8yKQB.
8. Phinney DG, Sensebe L. Mesenchymal stromal cells: misconceptions and evolving concepts. Cytotherapy. 2013;15(2):140-5; doi:
10.1016/j.jcyt.2012.11.005.
9. Sterile Injectable Drugs Market to Reach US $901.3 Billion by 2025, Globally: Transparency Market Research. Transparency Market Research. 16 Jan.
2018. Web.
10. Twose Lluis, Pharma’s Almanac, Grifols, TerminalSterilizationforParenteralDrugs:FindingtheRightCDMOPartner,October 2, 2018 PAP-Q3-18-CL-015.

f) Describe the storage and distribution of pharmacopeia grade water for injection (WFI).

Water for injection (WFI) is a vital resource in the pharmaceutical industry, used for vaccinations, cleaning, sterilization. It is generated, stored, distributed using
heat exchangers for P-line applications. Hexonic technology uses thermal distillation for WFI generation, ensuring its microbiological integrity. P-line heat exchangers
are commonly used for heat transfer, involving preheating, regenerative heating, final condensation. The P-Line Design uses double tubesheets, triclamps,
connections, with Viton, Silicon materials. The WFI must be stored, distributed appropriately, with user-specified parameters during the project design phase. A
potential approach for implementing a WFI storage + distribution system is maintaining a consistent temperature range of 80°C - 85°C.

The temperature is regulated through the utilization of a P-line heat exchanger, in which the shell side is supplied with either technical steam or water.

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https://hexonic.com/en/applications/pharmaceutical-industry/wfi-hot-storage-and-
distribution/#:~:text=One%20of%20the%20implementations%20of,supplied%20in%20the%20shell%20side.

INOXPA supplies components for PW/WFI distribution loops in the pharmaceutical industry, including centrifugal pumps, regulating valves, check valves, and
overflow valves. They also provide fittings and heat exchangers to prevent contamination.

https://www.inoxpa.com/uploads/document/Fitxa%20tecnica/Processos/Lazo%20de%20agua%20purificada/FAphLoops%20%20PW_WFI.1_EN.pdf

Reverse osmosis, electrodeionization, ultrafiltration.

Membrane-based WFI systems offer cost advantages over distillation.

https://www.evoqua.com/en/evoqua/products--services/high-purity-systems2/packaged-high-purity-water-systems/sdrx-storage--distribution-system/

Ensuring adequate sanitization is of utmost importance in preserving water quality (hot water, ozone sanitization).

Storage +distribution systems for PW /regular sanitization/ + WFI /thermal s. using ozone/.

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https://cm-systems.pl/en/products-and-services/storage-distribution-systems#:~:text=WFI%20water%20is%20usually%20stored,the%20peaks%20in%20water%20use.
1) Chemical sanitization:

2) Thermal s.:

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 3) S. -ozone:

WFI storage and distribution systems should be periodically sterilized at the temperature of ≥ 121 ° C (s. using superheated water or pure steam).

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Parallel Loops – Single Tank.

Hot storage – self-contained distribution.

Single point of use – steamed.

Point of use installed in sub-loop.

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/242 words count without links/ref/

Bibliography:

1. Biocell-Pharma, Water For Injection System — WFI Water System, https://www.biocell-pharma.com/products/wfi-water-for-injection-

system/?gclid=Cj0KCQjwsp6pBhCfARIsAD3GZuamhtkFni0BvGpfbh4xeHc4zDjVgsMzkvj0Z7WyMEPacB1cAIIsvHQaAu4kEALw_wcB
2. Cm-systems.pl, Pharmaceutical Water Storage and Distribution Systems, https://cm-systems.pl › products-and-services › storage-d..

2. Drug future, What is the packaging and storage of sterile water for injection?
https://www.drugfuture.com/Pharmacopoeia/USP32/pub/data/v32270/usp32nf27s0_m88870.html#:~:text=Packaging%20and%20storage%E2%80%9
4%20Preserve%20in,I%20or%20Type%20II%20glass.
3. eBioPharmaChem certificate GetReskilled materials, Pharmaceutical Facility Design Section 4-6 WFI Storage and Distribution,
https://learning.getreskilled.com/pluginfile.php/2267979/mod_resource/content/3/4-6%20WFI%20Storage%20and%20Distribution.pdf
4. European Medicines Agency, Guideline on the quality of water for pharmaceutical use, https://www.ema.europa.eu › scientific-guideline.

5. Hexonic, WFI hot storage and distribution, https://hexonic.com › pharmaceutical-industry › https://hexonic.com/wp-

content/uploads/2021/07/HEXONIC_P-LINE_EN_CMYK_2023-05-04-1.pdf.

6. INOXPA, Loops of purified water (pw) and water for injections (wfi), https://www.inoxpa.com › document › Processos

7. JBTC Production of Water for Injection for the Pharmaceutical and Bio-Pharmaceutical Industries, jbtc.com

https://www.jbtc.com › uploads › sites › 2021/09 › https://www.jbtc.com/foodtech/wp-content/uploads/sites/2/2021/09/Water-for-Injection-WFI.pdf.

[email protected]

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