The document discusses generic drug performance and quality in Pakistan. It notes that while generic drugs can significantly lower drug prices, they must demonstrate the same therapeutic effects as innovator drugs. Ensuring drug quality is complex and requires integrated multidisciplinary approaches. The drug regulatory authority of Pakistan (DRAP) is approving many generic drug applications but faces questions about the quality of the drugs it supervises due to limited resources and testing capabilities compared to agencies like the US FDA. Improving post-marketing quality surveillance and compliance with good manufacturing practices is important to ensure drug safety and availability.

1. GENERIC DRUG PERFORMANCE
Enhanced Approach to Grip Quality Signals in Post Marketing
Roohi Bano Obaid, R. Ph., M. Phil
Civil Services Officer/ Deputy Director
Drugs Regulatory Authority of Pakistan
Government of Pakistan
Member, ISPE & Member PDA
Disclaimer:
It is personal point of view written in best of
professional knowledge and experience of
regulatory sciences. It is not an obligation to
agree by the organization or association to which
I belong (Oct 22nd 2017)
Even in developed modern world, up to 10 to 90% of drug prices goes down upon creating an
environment that provides a leveled field of competition for generic drugs that represent copy of reference
innovator drugs. Generics promise the same therapeutic performance as demonstrated by the innovator
drug product. This great promise is examined and verified by the Government before it reaches to the
patients. Placement of controls during manufacturing and compliance of predefined quality attributes
support the best to have confidence on claim and promise of the manufacturer. On the other hand, the
equal or comparable drug release pattern from formulation and its permeability in the biological system
are the ultimate expectations. It sometimes may emerge as a real challenge among various therapeutic
groups and chemical molecules, both at the end of manufacturer and regulatory agency.
Health and life are the essential theme for a patient,
his/her family, healthcare professionals, Government
and global efforts among the Governments on both
humanitarian and economical grounds. If a dose does
not deliver its promise, it may sometime end up in
taking life of an individual or making life of the
individual more miserable by causing adverse
reactions. Assessment and review of generic drugs
application is a complex process and not so simple. It
requires integrated multidisciplinary approaches
based on critical thinking to assess the potential of
failures in the commitment profile of safety, efficacy
and quality. The formulation of drug products of different companies is not similar. In this way, existence
of different intra-molecular forces in different formulations contribute significantly in shaping and
sustaining the release profile of drug throughout their shelf life. The data of world leading and well
equipped regulatory agency of the world i.e. Food & Drug Administration of United States of America
(US-FDA) reveals the underline level of care for the human beings as they reached to approval of 763
US-FDA equipped with innovative
& qualified tools, highly skilled
human resources utilizes the best
approaches but are behind from
the FOUR (04) figure number in
the approval of generic drugs,
whereas, DRAP Pakistan is
interestingly competing to be in
FIVE (05) figures. Sincerity scale of
DRAP in public safety and drug
quality affairs needs no comment

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generics in the year 2017. This is competing to double from the year 2014 due to increase in human
resource and utilizing the best tools based on statistical model and scientific approaches. While highly
incomparable Drug Regulatory Authority of Pakistan (DRAP) in terms of human resource, knowledge
bank and tools started granting approval of generic drug products applications around to five figures.
Confidence on DRAP’s drug registration process is badly affected all around, e.g. even North African
countries deny giving respect to DRAP drugs registration. A number of regrets are putting serious
questions on the quality of drug products being supervised by DRAP and consumed by fellow citizens.
Post marketing quality surveillance requires regular compliance inspection of manufacturing site and
product quality surveillance. These include collection and review of complaints, adverse drug reactions
and epidemiology. The ultimate intent of a regulatory agency between the lines is to ensure availability of
the drugs and consumer safety. Quality attributes have a tremendous potential to navigate the corridor of
uncertainty in terms of sudden shortage and/or safety crisis. For example, if an injectable product carries
particles, it is quite possible that corrective action at manufacturing site may take a long time to end up
dryness in market due to absence of other manufacturer for the same product. Likewise, if a tablet of
narrow therapeutic ratio fails in its release profile due to losing control strategy associated with supplier
of excipient or API; it can create shortage and put life of patients on the mercy of heart breaking time.
A consumer usually cannot detect (through smell, touch, or sight) that a drug product is safe and will
perform well. Traditional and routine quality testing of drug may verify the level of compliance to its
approved specifications in terms of its attributes, whereas, testing alone cannot give assurance of safety,
efficacy and quality of products. Quality needs to be built in during the whole process starting from
selection of supplier and raw/ starting materials, manufacturing practices to delivery of products for uses.
Current Good Manufacturing Practices (cGMP) is a component of Quality System for ensuring that
products quality are controlled according to standards and designed to reduce the possible risks in any
pharmaceutical production that cannot be eliminated through testing afterwards. It is important that drugs
are manufactured under conditions and practices required by the cGMP standards to assure that quality is
fabricated into the design and manufacturing process at every step. Manufacturing facilities need to be in
good condition, equipment need to be properly maintained and calibrated, employees should be qualified
and fully trained, manufacturing processes should be reliable and reproducible and their efficient
integration will assure safety and efficacy of drug products.
A storm of unreasonable testing by regulatory authority, weakest understanding on the standards required
for reliable testing and declaring a product as “standard quality” based on reduced testing across the
central and all its provincial institutions is another indicator to see the capacity of the leaders engaged in

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shaping the future of pharmaceutical quality in the country. Registering the court case upon non-
conformance of any attribute found by laboratory (which is not qualified for any desired standard) is
another dilemma for the licensed manufacturers to face lengthy, hectic and disgraceful regulatory
consequences. The US-FDA having a number of testing facilities across the US tested about 4000 drugs
in past 10 years. The selection criteria of product start from complaint pattern about reduced effectiveness
to whistle blowing of internal (regulators) or external (scientists) experts. Sometimes GMP concerns and
potency concerns of certain drugs require attention for specific testing. The most prescribed drugs and
first generic versions are also covered under priority. It is not out of the context to understand the
limitations of testing. In most of the cases, testing is not capable enough to catch physician or patient
complaints, GMP, process variability, validation and recalls issues and the product meets or passes
quality standards upon testing. US-FDA's state of the art laboratories found 1.1% of the drug products in
10 years to be deviated from the acceptable standards. In recent past year US-FDA tested 84 finished drug
products from all across the United States while DRAP associated laboratories crossed five (05) figures in
a year with regard to testing of finished drug products. The objective of testing in Pakistan is somehow to
declare products of standard quality for the Government Supplies and to bring them in a line, where one
cannot differentiate the compliance level of GMP standards. Sampling and testing figures are always put
on the top in DRAP’s presentations, speeches and testimonies to build a wrong perception convincing the
Public and Parliament about their performance and considered as a progress indicator for drug quality.
This wrong perception is very gently and nicely being protected by the Authorities since decades. On the
other hand, without realizing the scientific fact of matter and deficiencies in testing and sampling process,
it hangs as a sword on the manufacturers to face rigorous consequences upon non-conformance of any
attribute of any of their product.
It would have been good if attempt is done to shape the thinking process in a way that impacts in
strengthening the promise of label claim. Promotion to generate genuine complaints with regard to drug
product performance, its evaluation and verification on the basis of super science will help to uncover the
potential risks above the level of residue. It is the time to
understand the relation among what we know, what we can
and what we should not; to construct the road for progressive
and smart traveling towards making drugs Safe, Effective and
of Quality.
It is the time to understand the
relation among what we know,
what we can and what we should
not; to construct the road for
progressive and smart traveling
towards making drugs Safe,
Effective and of Quality.