Goods Manufacturing Practice

This document discusses Goods Manufacturing Practice (GMP) and its significance in ensuring the safety and efficacy of drugs and other products. It highlights the violations by Sun Pharmaceuticals and the corresponding FDA regulations. The document also covers performance validation and acceptance criteria for maintaining product quality. The subject is relevant to the pharmaceutical industry and quality control.

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GOODS MANUFACTURING PRACTICE
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Part 1
Food and Drug Administration (FDA) is a body responsible for offering protection to public
health through efficacy assurance, security and safety of human and drugs, cosmetics, medical
devices, food supply and products, biological products emitting radiation (FDA, 2018). On the
other hand, Sun Pharmaceuticals industries are focused with manufacturing and marketing of
pharmaceutical ingredients such as drugs. Moreover, in December 2015, FDA sent a warning
letter to Sun Pharmaceuticals Ltd on violating the FDA regulations on Good Manufacturing
Practices (GMP) as well as violation of record keeping and documentation laws (FDA, 2018).
Since FDA advocates for protection of public health, such regulations are critical to govern
manufacturers in various industries.
Furthermore, with regard to Deficiency 4, Sun Pharmaceuticals firm is considered to have failed
not only establish but also to offer documentation of accuracy, reproducibility, sensitivity and
specificity of test methods as per FDA regulations. Moreover, validation in analytical method
demonstrates the suitability of the testing procedure that is intended. Thus method validation
gives outcomes that are vital in assessing the quality, consistency and reliability of analytical
results. Thus the firm failed to evaluate accuracy on dissolution test method for (b) (4) tablets
during validation. On the other hand, from the FDA code of regulations based on the above
problems, the operating law in section 211.110 is based on production and process control.
Moreover, to ensure batch integrity and uniformity of drug products, there should be an
establishment of written procedures and then followed by tests, in-process control and
examination procedures. Consequently, such control procedures should be established for
monitoring the output as well as to also validate the performance of the manufacturing processes
which causes variability in in-process material as well as the drug product. In addition, such

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control procedures comprise of; disintegration time, bio burden testing, dissolution time as well
as rate, clarity, solutions pH and completeness.
On the other hand, Sun Pharmaceuticals failed in evaluating capacity of separating unidentified
late eluting peaks (b) (4) injection, (b) (4) ml or (b) (4) mg and HPLC (high performance liquid
chromatography). Additionally, the response of the firm in October 2014 stated that revised
method comprising (b) (4) chromatographic run time detection of late eluting peaks got approval
by FDA in 2014. However, from observations and scrutiny by FDA, it was noteworthy that there
was failure in documentation and the method was too inadequate and not promptly after the first
detection and investigation of impurities. In addition, the FDA and GMP were violated. Notably,
the GMP rules that are applicable to these problems include Laboratory Controls which involves
testing and release for redistribution. Thus such documentation and validation can be
accomplished in accordance with section 211.194 (a) (c).
Moreover, laboratory test would be utilized where any sampling and testing that is conducted has
to be descried in written steps which must include sampling method as well as various units
found in a batch. Furthermore, the instruments’ calibration, gauges, apparatus as well as
recording devices at right intervals in accord with conventional written program that has specific
directions, precision, schedules and limits of accuracy should be key to manufacturing.
Additionally, an appropriate number of batches of very drug need to be tested for determination
of correct expiry date thus a record of such information are maintained. Likewise, accelerated
studies in combination with fundamental stability information on various components, closure
system of a container and drug products are vital for supporting tentative dates of expiration.
In addition, during inspection of microbiology laboratory, it was observed that several sterile
gloves that were intended for use in the manufacturing of sterile products were immersed

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partially in (b) (4) medium. Furthermore, it was worth noting that the investigator’s findings
disclosed that fingers of the gloves were not subjected to full immersion. This was rather a
violation of FDA regulations and laboratories inspection for quality control on Testing Procedure
for Sterile (b) (4) Gloves. Thus according to FDA CRF 211 regulations, the applicable law in
regard to these problems is majorly Production and Process controls. Thus it is noticeable that to
control microbiological contamination of drugs, there should be suitable written procedures that
are designed for preventing objectionable microorganisms that may penetrate to drug products
that are not required to be sterile, thus such regulations need to be fully established and strictly
followed.
On the other hand, suitable written procedures which are designed for preventing microbial
contamination for drug products that are intended to be sterile should as well be fully established
and strictly followed as per the regulations. In addition, such procedures includes validation of
various aseptic as well as sterilization processes. Moreover, written procedures need to be
established and keenly followed in order to prescribe a system vital for batches processing that
fail to conform to specifications or standards and also disciplinary actions to be taken to ensure
which reprocessed batches to follow all set standards, characteristics and specifications.
Part 2 - Bicalutamide USP Monograph
Performance parameters refer to quality that that can be quantified by numerical values and thus
characterizes a given aspect (Beckman et al., 2016).

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Performance Validation Scope
Notably, performance validation is normally useful in verifying that equipment executes
consistently and correctly throughout a series of parameters in the entire range design. In
addition, regulations contain basic good manufacturing practice that aids in preparations of drug
products that are consequently vital for administration to animals as well as humans. Moreover,
various activities are thus conducted on systems critically to demonstrate and document that the
equipment in question is able to perform its functions as intended within the variable limit
process for a specific product.
Performance validation
It is worth noting that testing comprises various activities like sterilization, verification,
sanitization and examination, accuracy, reproducibility and specificity. In addition, for a precise
test, at least three runs of successful consecutive tests are mostly used. Furthermore, the process
may be accompanied by some system challenges on the operating limits, however, these
challenges do not lead to any failure. Thus this testing provides high level of confidence that the
equipment would properly function even in adverse conditions. Additionally, the normal
expectations for the performance are given as documented verification facilities, requiring,
connection of system and equipment together. Thus the performance is therefore effective and
repetitively in accordance to the approved process method specifications of the product.
Additionally, the verification of performance parameters should ensure that the User
Requirements Specifications (URS) are served and fully complied with. Moreover, performance
validation represents the justification of an equipment or system as either qualified or not. In
addition, performance validations offers the reasons for incorporating a series of testing to

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simulate option of production process and also provide assurance that the operating document
and system are capable of successive process of validation activities.
Acceptance Criteria for Performance Parameters
To ensure that the purity and quality of a product is maintained according to the Code of Federal
Regulations, acceptance criteria must be developed. Acceptance criteria for testing and sampling
conducted by quality control unit is adequate and assures which batches of drug products attain
appropriate specification as well as criteria for quality control as a requirement of approval and
release (Alsmeyer et al., 2015). It is notable that quality control criteria includes suitable
acceptance level or rejection levels. Thus the acceptance criteria for pharmaceutical products
commonly are multi – level. Since there are more sophisticated acceptance criteria, capability
measures and traditional SPC strategies may lead to short fall or erroneous in providing an
efficient assessment of product risk (Alsmeyer et al., 2015). Moreover, a more applicable method
of analysis is required to give a reliable understanding on how a product can fulfil the
requirements for quality attributes. For instance, dissolution testing and dosage uniformity in
pharmaceutical analysis majorly use various tested units and therefore follows step – wise
acceptance criteria as in monographs such as USP.
Experimental Design for Performance Parameter
It is worth noting that good quality control in pharmaceutical drugs represent acceptably desired
clinical attributes and low risk of any failure. On the other hand, a quality design refers to
systematic approach aimed at developing from set objectives in understanding product and
process control as well as risk management techniques (Peraman, Bhadraya & Padmanabha
Reddy, 2015). Moreover, for design experiments, in agreement with the basic requirements of

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FDA as well as CFR regulations as regard to design space, method operable design region
(MODR) thus can be developed as a method of development phase that could thereby act as a
source of cost effective and robust method (Tang, 2011). Furthermore, MODR allows for
flexibility in several input methods parameters for provision of expected response and criteria
without resubmission to FDA. Thus to design an experiment by quality by design (QbD), the
following key steps are necessary, firstly, Target measurement is taken. In this, an appropriate
measure is taken and developed based on QTPP and CQA (Peraman, Bhadraya & Padmanabha
Reddy, 2015). Secondly, analytical technique is selected as desired and performance criteria
conducted. Thirdly, risk assessment is done for sample variation and operating parameters by
risk assessment tools like FMEA (Tang, 2011). Fourthly, method validation is conducted to
examine various interactions through design space. Ruggedness and robustness of the method is
determined. Again in the next stage control strategy is determined for performance criteria and
finally continual improvement is done where performance method is monitored.

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Bibliography
Alsmeyer, D., Pazhayattil, A., Chen, S., Munaretto, F., Hye, M. and Sanghvi, P. (2015).
Acceptance Probability (P a) Analysis for Process Validation Lifecycle Stages. AAPS
PharmSciTech, 17(2), pp.516-522: doi: 10.1208/s12249-015-0338-5
Beckman, A.T., Nalagatla, A.K., Hibner, J.A. and Shelton IV, F.E., Ethicon LLC, 2016. Surgical
apparatus configured to assess whether a performance parameter of the surgical apparatus is
within an acceptable performance band. U.S. Patent Application 14/633,546.
FDA (2018). CFR - Code of Federal Regulations Title 21. [Online] Accessdata.fda.gov.
Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?
CFRPart=211 [Accessed 8 May 2019].
Peraman, R., Bhadraya, K. and Padmanabha Reddy, Y. (2015). Analytical Quality by Design: A
Tool for Regulatory Flexibility and Robust Analytics. International Journal of Analytical
Chemistry, 2015, pp.1-9: doi: 10.1155/2015/868727
Tang, Y. (2011). Quality by Design Approaches to Analytical Methods. FDA Perspectives.
[Online] Available at: https://www.fda.gov/files/about%20fda/published/Quality-by-Design-
Approaches-to-Analytical-Methods----FDA-Perspective--Yubing-Tang--Ph.D.--October--2011--
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