Disclaimer: It is purely personal point of view written in the best of professional knowledge and experience of dealing with affairs of regulatory sciences as Federal Regulator. In any way, it is not an obligation to agree by the organization or association to which we belong. The intent of writing is to sensitize culture of reading, learning, arguing and writing. Feedback: All critics, comments and questions will be welcome
From Command Line to Reporting Line: The Diary of a First-Time EM
Pakistan's Regulatory Approach: Can Quality of Drug be assured through Testing in Government Laboratories
1. Pakistan’s Regulatory Approach
Can Quality of Drug be assured through Testing in Government Laboratories?
Obaid Ali & Roohi B. Obaid
Planting quality in manufacturing of drugs and its secure delivery to the patient is a real challenge and remains a
concern all around. Inability of the intellectuals and Government leadership (Federal Government, generally
Provincial Governments and particularly the Punjab Government) to understand the phenomenon of drug quality
is certainly amazing and a reason of great distress for real professionals. It is considered that drugs are safe, if
there is no report of people death and of efficacy, if people get relief from it. On the other hand, government
laboratories check for presence of therapeutic agent in samples in the right amount and consider this checking
sufficient to declare that we have safe and efficacious drug. All the reasons exist to suggest that the both
assumptions are nothing but myths.
It is as simple as if someone could understand that why dozens of times lower price drug is not imported by
United Kingdom (UK) whereas, it is tested in UK laboratories and found of standard quality. The Governments
especially Punjab Government while neglecting the
fundamental affairs of regulatory science is spending a
disproportional amount of public money and putting
extensive resources into drug testing. There is no
regulatory impact analysis (RIA) document available to
justify such unrealistic expenditure. It would have been
very good to hear from real subject matter experts instead
of experts of other professions and RIA should have been carefully done well before time. However, it is not too
late to respect the tools of modern science, come out from ego and do the best with all honesty.
For the sake of clarity, let’s take a scenario as an example where food stuff being cooked on roadside in an open
environment and in a five star hotel kitchen. Remember that the material, chef and the recipe are same in both
cases. Upon testing of samples from both food stuff, if a piece of hair is found in stuff coming from a five star
hotel while there is no issue in the sample of stuff coming from roadside, how would you deal with them? Surely
your trust will not breach on a five star hotel and you will treat presence of hair as an isolated incident that may be
covered under residual margin of error. On the other hand, if you declare food stuff of roadside as a standard
quality and allow using for a large population, there is no need to comment further on wisdom. On the presence of
hair, if we accuse the five star hotels and pull up in the court process, it would be unreasonable, worst and
inconsistent with the fundamental approach of regulatory sciences.
If someone could understand that why
dozens of times lower price drug is not
imported by United Kingdom (UK)
whereas, it is tested in UK laboratories
and found of standard quality.
2. Can Quality of Drug be assured through Testing in Government Laboratories? Page 2 of 4
Obaid Ali & Roohi B. Obaid Karachi the 20th
Nov 2017
Be aware that the writers are talking about the drug product taken to save the precious life of human beings.
Equipment, manufacturing process, quality of raw materials used to manufacture one similar product are not
exactly same in different industries. To demonstrate that someone is capable to manufacture quality drug requires
a lot of scientific studies and data that is certainly reviewed by number of different experts from regulatory
authority to decide its reasonable equivalency in therapeutic effect within acceptable bracket of consumer safety
and other claims conclusively in the interest of protection and advancement of public health.
It was a time long ago when extensive testing was relied upon, to guarantee a quality drug and all the quality
affairs revolved around classical tool (Testing). Later on with the experience and expanding knowledge, it came to
bright that the manufacturing process have a greater impact on drug quality, hence, in-process controls were
introduced and they became the part of the regulation. Further
moving upward on the ladder of age, the limitations of sampling
was realized in representing the whole batch. Moreover, the
limitations of testing surfaced and established that testing of 20
units of a batch consisting of millions of units cannot assure the
quality of every unit of the batch. Resultantly, emphasis was
extended, reshaped and focused more on the product
development, process understanding and control strategy to
achieve consistency within a batch, time after time and batch
after batch. Studies conducted by hospitals to collect the
evidence of clinical outcome among different generics or between generic and innovator may not give sound
scientific strength to decide drug equivalency or its associated safety. For example, if you judge the quality of a
perfume by its smell, you may not be able to conclude its life span, impurities it carry etc. and sometimes this
approach might end up in disaster (a lot of examples that took lives of individuals have already been experienced
by this world).
Independent and integrated regulatory reviews under Good Review Practices (GRP) as well as regulatory
inspections of manufacturing sites under Good Manufacturing Practices (GMP) standards to determine the
strength of product and manufacturing capacity are indispensible. So, without understanding the entire
manufacturing process and mechanism to keep controls efficient throughout the manufacturing, no one will be
able to say that drug is consistent in the entire batch in terms of purity, right dose and right delivery of drug inside
the body and is without unreasonable contamination of germs, particles and traces of other drugs. Such oversight
also ensures elimination of any potential mix up with other drug, same drug of different strength or with sorted
(defective) drug during the each and every step of the manufacturing and distribution process until it reaches to
the patient.
Testing of 20 units of a
batch consisting of
millions of units cannot
assure the quality of every
unit of the batch.
3. Can Quality of Drug be assured through Testing in Government Laboratories? Page 3 of 4
Obaid Ali & Roohi B. Obaid Karachi the 20th
Nov 2017
It is necessary to be abreast of the fundamental dimensions that categorically spell time and again about
limitations of compendia procedures of testing. In most instances testing is done on a small sample of a batch (for
example, a drug manufacturer may test 100 tablets from a batch that contains 2 million tablets), so that most of the
batch can be used for patients rather than destroyed by testing. Therefore, it is important that drugs are
manufactured under conditions and practices required by the GMP regulations to assure that quality is built into
the design and manufacturing process at every step. Facilities that are in good condition, equipment that is
properly maintained and calibrated, employees who are qualified and fully trained, and processes that are reliable
and reproducible, are a few examples of how GMP requirements help to assure the safety and efficacy of drug
products. Let us take another example of injectable products which are supposed to be free from microorganism
known as sterility test. It should be recognized that the referee
sterility test might not detect microbial contamination, if present in
only a small percentage of the finished articles in the lot because the
specified number of units to be taken impose a significant statistical
limitation on the utility of the test results. Global Bible of testing of
drugs (Pharmacopoeia) itself state that these procedures are not by
themselves designed to ensure that a batch of product is sterile or
has been sterilized. A state of sterility assurance can be established
only through the use of validated sterilization process or aseptic
processing, if any, under appropriate GMP and not by reliance
solely on sterility testing.
The intent of this article is not to eliminate the role of regulatory
laboratory in the quality oversight but need to understand its
inherent limitations. The largest leading regulatory authority of the
world, United States-Food and Drug Administration (US-FDA)
having a dozen of state of art and fully equipped qualified testing
facilities across the USA, tested about 4000 drugs in 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. US-FDA's laboratories found 1.1% of the drug products in 10 years to be deviated from the
acceptable standards and found out of specification (OOS). Responsible managements were given hands for
assistance in timely improvement to avoid any unreasonable drug shortage. Voluntary pursuance to go for root
cause analysis, corrective and preventive action always remain action of choice instead of opting and imposing
regulatory or enforcement actions. In the light of facts described here diversion towards criminal proceedings or
misuse of power upon OOS results in Pakistan may be reviewed by looking at the data of modern world that is
being emerged with super science.
We have a lot of
experience to see
graveyard of scientific
instrument in public
sector. Till date neither
World Health
Organization (WHO) nor
any other international
agency recognizes any
Government laboratory of
Pakistan for testing of
drugs giving credible
results.
4. Can Quality of Drug be assured through Testing in Government Laboratories? Page 4 of 4
Obaid Ali & Roohi B. Obaid Karachi the 20th
Nov 2017
The important issue of the laboratory is the reliability of the results, their reproducibility upon retesting in the
same laboratory or other laboratory and auditability to back trace the data reaching to the conclusion for its
integrity. Beautifying the buildings and investment in equipment may give an aesthetic sense of development to
the common people but has no role in credibility of the results unless the systems are based on sound science. It is
very unfortunate to see the government
laboratories purchasing ruthlessly innovative
and highly sensitive equipment, while people
are not trained to drive and operate them. It is
as simple to elucidate the event that you buy
modern Mercedes car and allow someone to
learn driving on it, who does not know to drive a car before. We have a lot of experience to see graveyard of
scientific instrument in public sector. Till date neither World Health Organization (WHO) nor any other
international agency recognizes any Government laboratory of Pakistan for testing of drugs giving credible
results. Even countries of the North African region qualify WHO standards and are included in their list available
on the WHO website. From last four years, authorities have attempted to deceive the public consistently through
publication of false news and testimony before the Parliament that their laboratory is about to be qualified by
WHO.
It should be straight, simple and clear that the quality of medicines available in Pakistan could not yet gain respect
from any reference or world leading countries. There is no report available to exhibit or prove the quality (product
manufactured here in Pakistan, no matter it is from corporate giant or national small business) as per the standards
set down in the 21st
century. Knowingly or unknowingly use and promotion of government laboratories data about
quality of drug available in market is indeed a false perception. Remember and please be aware that regulatory
science is not so simple and small but complex and will be more challenging in the days to come. To ensure
public safety and quality of drug, we have no way left other than to enhance capacity of learning, de-learning and
relearning that could make our walk compatible with the modern science and get it trusted all around
Obaid Ali, R. Ph., M. Phil., Ph. D. Roohi B. Obaid, R. Ph., M. Phil.
Disclaimer: It is purely personal point of view written in the best of professional knowledge and experience of dealing with affairs of
regulatory sciences as Federal Regulator. In any way, it is not an obligation to agree by the organization or association to which we
belong. The intent of writing is to sensitize culture of reading, learning, arguing and writing. Feedback: All critics, comments and
questions will be welcome on obaidali1971@gmail.com (Nov 20th
2017)
To ensure public safety and quality of drug, we
have no way left other than to enhance capacity
of learning, de-learning and relearning that could
make our walk compatible with the modern
science and get it trusted all around.