Comprehensive Review of Good Manufacturing Practice in Pharmaceuticals

This report provides a comprehensive review of Good Manufacturing Practice (GMP) within the pharmaceutical industry. It begins with an overview of GMP's objectives, emphasizing its role in establishing quality management systems and ensuring the integrity of pharmaceutical products from raw material sourcing to final product distribution. The report details the importance of quality assurance, quality control, and adherence to Standard Operating Procedures (SOPs). The report also highlights the critical role of documentation, including record-keeping, internal audits, and hygiene practices. The second part of the report examines documentation practices, emphasizing the importance of authorized signatures, controlled documents, and the role of SOPs. The report then analyzes FDA warning letters, focusing on non-compliance issues and misleading advertising. A case study of a warning letter regarding the TOUJEO insulin glargine injection is discussed. The report concludes with a review of a drug recall, specifically focusing on Valsartan products and the presence of the NMDA impurity, and its implications for patient safety. The report references the Health Products Regulatory Authority (HPRA) website for the recall details, which is an essential part of the analysis. The report also mentions the recall letters issued to doctors and pharmacists.

Running head: REVIEW GMP
REVIEW GMP
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Answer1
Part a: The objective and the purpose of Good Manufacturing guideline is to provide a
structure by which the manufacturing companies can refer to and also get an appropriate
system so that the managing the quality in a company. The good manufacturing practices
covers all the aspects of the pharmaceutical production company so that there could be
covered the manufacturing of the products could cover all the aspects of collection of raw
materials, storage, keeping the products in the quarantine zones, labelling, keeping a
continuous checks on the quality of the drug products. The Good manufacturing practices
also aims at generating a structure for proper guidelines for maintaining and keeping the
Standard Operating Procedures, by which the company could keep a record of the drugs
which are coming and going out from the pharmaceutical companies. One of the important
part of the Good Manufacturing Practices include Quality management. In Quality
management there is an incorporating and linking of Quality Assurance or QA, Quality
Control or QC. The main purpose of the Quality management is proper handling and control
of Active Pharmaceutical Ingredient or API (International Conference of Harmonisation of
Technical Requirements for Registration OF Pharmaceuticals for Human use 2019). The
active pharmaceutical ingredient is an important part of any pharmaceutical product and any
deviation or breaching of the protocol has to be addressed and answered with proper
justification. From the good manufacturing practice, when handling the active pharmaceutical
Ingredient the proper equipment as well as the attire should be worn, to eliminate any kind of
contamination in the way of manufacturing process of any drug. Raw material selection as
well as the selection of active pharmaceutical ingredient is also an important aspect on the
basis of which the materials are accepted or rejected. The raw materials and API should be
taken from the approved vendors, and should be checked every time while preparation of the
drug. There are different parts of processing in a pharmaceutical company and some involved

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the mechanical processing of the drugs after it has been recovered or passed the test regarding
to the quality. There are different protocols when it comes to the processing of the materials
and drugs, for chemicals, plant extracts, herbal extracts and other products which are
processed through fermentation have different structure, which has to be in accordance with
guidelines. The documentation part is done by the quality assurance and the quality control
together, the batch manufacturing product are tested and recorded with batch to batch
maintaining the records. The documentation of each Standard Operating Procedure, Working
methods are recorded and has to be circulated towards the authorized person who is in charge
or the concerned person who is taking in control in that particular area. Internal audits are
another important parameters of self-inspection so that there could be less mistakes when
compounding all the data and progress updates. Furthermore, it is responsible towards the
personal maintenance of hygiene which is an essential part of the Good Manufacturing
Practice and quality assurance. Good sanitation and health habits and checking it is one of the
key parameters of Quality Management.
Part b: Any pharmaceutical plant has a part of documentation and records. The good
documentation practice is a way or method so that there is a continuous checks of records and
current implementation of any new procedure or machinery in the plant. By authorising and
assigning the documents, it keeps the check on the progress of the manufacturing unit and as
well as helps in maintaining batch records of a company (European Commission 2019). In
the section of 4.9, the any existing of new document which has been alerted has to be
circulated and signed. Good documentation Practice is an important part of quality assurance
which should be in accordance with the good manufacturing practice and in accordance with
the Good manufacturing practice requirements. In a pharmaceutical settings there are many
mediums by which documentation is done, it can be either hand written or in the electronic
media or it can be also photographic media. Any manufacturing pharmaceutical plant has a

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specific plan which has to be understood and documented. According to 4.1 section the
documents should be in appropriate control which means that the documents regarding the
operational procedures and other related documents should be given and allocated to the
concerned people and that should be acknowledged. Furthermore, the distribution of the
documents should be done with utmost care and the documents reach the concerned people
the documents have to be signed and attested by the authorised person (section 4.2, 4.3). It is
done in a manner so that the documents could keep a legitimate records of the process in the
plant can be administered and updated. One of the important concerns of the documentation
is the awareness of the important documents that has to be circulated and reported and that is
the reason the why the instructions need authorised signatures. Moreover, according to
section 4.5 the SOPs which are Standard Operating Procedures, Work Instructions as well as
methods have to design in the required structure and style which will be in compliance with
the good manufacturing practice. In the section 4.5, it is agreeable that there should
continuous follow up of the documents, so that all the new documents or any mechanical
procedure can be easily assessed by the workers of the plant. By the sections of the 4th
volume of the good manufacturing practices it could be understood the good documentation
practice all the documents are properly handled so that the documents are traceable and
handled with utmost care when propagating documented resource. The SOPs and other work
instruction of a company depend upon proper documentation and maintenance of records.
Therefore, the documentation provides proper evidences of the changes occurring in the
company. The good documentation practice enables to maintain proper quality control and
quality assurance. The batch manufacturing record is also a part of documentation that also
helps analysing and maintaining the quality of the products manufactured from the company.
According section 4.6, only some specific documents could be hand written with clarity and
for data entry. From the discussion it could be understood that good manufacturing practice is

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an integral part of good manufacturing practice, and it is a way to properly check of the
processes, distribution of products and circulation of any new information or guidelines in a
pharmaceutical company.
Answer 2
A warning letter is given by the food and drug administration whenever the there is a breach
or violation in the FDA regulations (Food and Drug Administration 2019). There are various
products that are displayed over the televisions and advertised openly that could give wrong
interpretation of using that product and could also possibly harm the consumer. Therefore,
the FDA issues warning letter, recall letters and other forms of investigation so that there is
no propagation of unsafe food or drug products given to the consumers. In the attached
document a warning letter has been mentioned. It is about TOUJEO which is an insulin
glargine injection (U-300). It is a subcutaneous injection which came in to the market.
However, this product has been introduced on the basis of direct to consumer broadcast
television, an advertisement which is entitled as “Mr Groove”. This particular ad has been
given warning letter on the basis of false and misleading claims provided by the product.
Furthermore, the warning letter has also described about the contraindications that were
found and reported which can cause episodes of hypoglycaemia. However, the main
objection from the FDA as it could identified that ad has not stated the possible risks and
contraindications of using TOUJEO. The hypoglycaemic episodes can also be fatal and send
a person to coma if immediate steps are not taken. Therefore, this ad has violated FD&C Act.
In other words the non-compliance is a term in which any product which has been marketing
on the basis of providing efficacy, however, the efficacy is fake or false from the claiming
output, from my view that product is non-compliance. However, the meaning of Non-
compliance can vary from person to person, for example milk is an essential for bone
development, however, when any person is lactose intolerant, for that person the intake of

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milk can be harmful, therefore, the administration of any food product should be cautiously
handled when it is mass produced. Therefore, whenever there is a product which is being
brought the limitations should also be highlighted and made aware to consumers, otherwise in
some case it might be fatal as well.
Answer 3
After viewing the Health Products Regulatory Authority website, a current drug has been
identified and an immediate investigation has been put forward. The products containing
Valsartan containing film coated tablet products have been found to be precautionary recall.
Valsartan is an active substance and ingredient which is used in medicinal products and other
tablets (Health Products Regulatory Authority 2019). Valsartan is one of the drugs to treat
high blood pressure and also used in the treatment of heart failure. This particular ingredient
has been found to be have an impurity known NMDA, N-nitrosodimethylamine (NMDA).
NMDA is a potential carcinogen when consumed, and it is also treated as a toxic substance
that could lead to fatality. It is also found as a by products in several industries. The website
updated Valsartan products to be under precautionary usage. However, the website has
advised that the patients should not abruptly stop taking medications before, prior
consultations. The reference of this product is QDR-H-18-381. The product is under current
investigation and the currently there are no evidence enough to prove potential harm to
patients. The present risk has been found on the basis of theoretical data and no empirical
evidence could be aligned with the data that has been found. Even though the recall letter has
been given to doctors and pharmacists and all other relevant health care professionals, the
patients have been advised to either switch to the alternative drugs or immediately go to the
pharmacist or a consulting doctor. The regulating body is currently investigating the affected
and the targeted medicines containing Valsartan and the investigating body will also confirm
the potential the harmful effects of NMDA. In another recall letter addressing to the doctors it

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has mentioned about NDEA or Nitosidiethylamine which contains Valsatran active substance
produced by Mylan manufacturing plant in India. This product contains this NDEA impurity
which can be produced as a probable carcinogen as well, and therefore, the current most of
the products are being recalled and update when the current investigation is completed. The
investigation will be made aware to the consumers, pharmacists and the doctors.

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References
European Commission, 2019. EudraLex - Volume 4 - Good Manufacturing Practice
(GMP) guidelines. Available at: https://ec.europa.eu/health/documents/eudralex/vol-4_en
Food and Drug Administration, 2019. Complaince & Enforcement. Available at:
https://www.fda.gov/food/complianceenforcement/default.htm
Health Products Regulatory Authority (HPRA), 2019. Valsartan Precautionary Recall.
Available at: http://www.hpra.ie/homepage/medicines/special-topics/valsartan
International Conference of Harmonisation of Technical Requirements for Registration
OF Pharmaceuticals for Human use, 2019. Good Manufacturing Practice Guide For
Active Pharmaceutical Ingredients. Available at:
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q7/
Step4/Q7_Guideline.pdf