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PHARMACEUTICAL ‘GOOD MANUFACTURING PRACTICES’ AND ‘GOOD

DISTRIBUTION PRACTICES’- A COMPARATIVE REVIEW OF DILIGENCE IN
REGULATORY STANDARDS

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 Indo American Journal of Pharmaceutical Research, 2016 ISSN NO: 2231-6876

PHARMACEUTICAL ‘GOOD MANUFACTURING PRACTICES’ AND ‘GOOD

DISTRIBUTION PRACTICES’- A COMPARATIVE REVIEW OF DILIGENCE IN
REGULATORY STANDARDS
Nirmal Kumar*, Dr (Prof) Ajeya Jha
Department of Management Studies, Sikkim Manipal Institute of Technology, Majhitar, Sikkim, India-737132.
ARTICLE INFO ABSTRACT
Article history The objective of the study is to compare the persistence of provisions of quality systems
Received 30/12/2015 prescribed for pharmaceutical manufacturing and distribution i.e Good Manufacturing
Available online Practices (GMP) and Good Distribution Practices (GDP). Method: The approach shall be
31/01/2016 exploratory studies, based on regulatory standards on ‘Good Manufacturing Practices’ and
‘Good Distribution Practices’. These practices are regarded as quality system during
Keywords pharmaceutical manufacturing and distribution operations respectively. The quality system
GMP, guidance have been issued by various agencies like, USFDA, EMEA and WHO. Result:
GDP, There is more emphasis on maintaining quality system during product manufacturing process,
SCM, whereas that during distribution process is not elaborative. The global pharmaceutical
Pharmaceutical Quality, regulators have invoked adequate provisions to ensure quality system during manufacturing
Pharmaceutical Product. process which is more rigorous as compared to that during distribution process. Conclusion:
Each pharmaceutical manufacturer should design suitable quality system that shall take care
of product quality during their plant operation as well as distribution operation.

Corresponding author
Nirmal Kumar
Department of Management Studies,
Sikkim Manipal Institute of Technology,
Majhitar, Sikkim, India-737132.
nirmal.quality@gmail.com

Please cite this article in press as Nirmal Kumar et al. Pharmaceutical ‘Good Manufacturing Practices’ and ‘Good Distribution
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Practices’- A Comparative Review of Diligence In Regulatory Standards. Indo American Journal of Pharmaceutical
Research.2016:6(01).

Copy right © 2016 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
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Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Vol 6, Issue 01, 2016. Nirmal Kumar et al. ISSN NO: 2231-6876

INTRODUCTION
Pharmaceutical Good Manufacturing Practice (GMP) is a manufacturing, packaging and testing practice that helps to ensure
in built quality product. Good manufacturing practices (GMP) is a part of quality assurance which ensures that products are
consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing
authorization.
The effective implementation of GMP entails deep knowledge about the different components of GMP that should be
incorporated form the inception of the manufacturing building and product development till the production.
As per WHO, Good Distribution Practices (GDP) is a part of quality assurance which ensures that a medicinal products is
maintained throughout all stages of the supply chain from the site of manufacturer to the pharmacy or person authorized or entitled to
supply medicinal products to the public. The pharmaceutical firms in general set up a combination of Quality objectives that can be
achieved only through careful planning and implementation of QA system and practical implementation of GMP and GDP.
Most of the countries of world have legislated that pharmaceutical companies must follow GMP and GDP procedures
through their own guidelines that correspond with the law of land. Only few countries have separate GDP regulations and the
guidance for distribution are invoked in GMP regulations only.
Individual manufacturing firms have to obtain market authorization declaration to follow the quality and distribution norms.
Appropriate certificate or license issued by the competent drugs regulatory authority for the purpose of marketing or free distribution
of a product after evaluation for safety, efficacy and quality. The customer may accord the qualification i.e marketing authorization
after quality audit. Different forms of marketing authorization provisions are provided to ensure that right products are distributed in
that customer country under the contractual agreement. The holder of a manufacturing authorization must manufacture products with
predefined quality standards, so as to ensure the medicinal products are suitable for the intended use, comply with the requirement of
marketing authorization and are safe.
Quality System is perceived as the sum of all aspects of a system that implements quality policy and ensures that quality
objectives are met as per aspiration of stakeholders throughout the pharmaceutical operations, manufacturing as well as distribution.

REVIEW OF GOOD MANUFACTURING PRACTICES:

The GMP guidelines are not rigid instructions on how to execute pharmaceutical production process. GMP is a set of general
principles that must be observed during manufacturing operation. When a company is setting up its quality program and
manufacturing process, there may be several ways it can conform to the GMP requirements. It is individual company's responsibility
to determine the most effective, consistent and efficient quality operation.
GMP is mainly managed by pharmacist and chemist and their key result areas include maintaining product purity, identity,
safety, quality, efficacy etc.
Although many countries have developed local drug regulatory requirements, many also rely on the World Health
Organization recommended GMP (WHO GMP) for pharmaceutical products issued in the form of Technical Report Series(TRS)
bearing specific reference numbers. Regional requirements have also appeared with application to several countries. Examples of
these include the following.
a. Pharmaceutical Inspection Convention Scheme (PIC/S) GMP:
b. Association of South-East Asia Nations (ASEAN) GMP:
c. Code of Federal regulations (CFR) of United States Food and Drug Administration :

The guidance issued by USFDA, consistently ensures the quality of drug products by regularly monitoring drug
manufacturers' compliance with its Current Good Manufacturing Practice (CGMP) regulations. The CGMP regulations for drugs
contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, controlling and packing of
a drug product. The cGMP is mainly covered in subparts A to K.
Current Good manufacturing Practices (cGMP) for finished pharmaceuticals as per US-Code of Federal Regulations (21 CFR
Part 211) have ben described in subparts ranging from A to K :

SUBPART A — General Provisions

SUBPART B — Organization and Personnel
SUBPART C — Buildings and Facilities
SUBPART D — Equipment
SUBPART E — Control of Components and Drug Product Containers and Closures
SUBPART F — Production and Process Controls
SUBPART G — Packaging and Labeling Control
SUBPART H — Holding and Distribution
SUBPART I — Laboratory Controls
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SUBPART J — Records and Reports

SUBPART K — Returned and Salvaged Drug Products
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d. European Economic Community (EEC) guide to GMP:

This guidance paper is unanimously accepted for manufacturing of medicinal products in European countries.
The rules governing medicinal products in the European Union" contains guidance for the interpretation of the principles and
guidelines of good manufacturing practices for medicinal products for human and veterinary use.
EU Good manufacturing practice (GMP) Guidelines (through EudraLex - Volume 4) has three basic parts.

Part I - Basic Requirements for Medicinal Products.

Chapter 1 Quality System

Chapter 2 Personnel into operation
Chapter 3 Premise and Equipment
Chapter 4 Documentation
Chapter 5 Production ( Manufacturing and Packaging Operation)
Chapter 6 Quality Control Laboratory
Chapter 7 Outsourced contractual activities
Chapter 8 Complaints handling and Product Recall
Chapter 9 Self Inspection Programme

Part II - Basic Requirements for Active Substances used as Starting Materials.

1. Basic requirements for active substances used as starting materials

Part III - GMP related documents.

Site Master File (SMF)

ICH-Q9 Quality Risk Management
ICH-Q10 Note for Guidance on Pharmaceutical Quality System
MRA Batch Certificate
Template for the 'written confirmation' for API for European Union for medicinal
products for human use (Version 2, January 2013)
Guideline on setting health based exposure limits for use in risk identification in the
manufacture of different medicinal products in shared facilities
Guidelines on the formalized quality risk assessment for ascertaining the appropriate
good manufacturing practice for excipients of medicinal products for human use

The core quality system of Current Good manufacturing Practices (cGMP) is implemented by a set of standard operating
procedure (SOP) which comprise of following QA elements:

1. SOP for SOP preparation, issuance handling and revision

2. Change Control and Change Management
3. Deviation control and Management
4. In-process testing and control
5. Training of plant personnel
6. Annual Product Quality Review
7. Internal Audit ( Self Inspection Programme)
8. Handling of product complaint
9. Handling of product recall
10. Corrective Action and Preventive Action
11. Product Release ( In process Material Release, Semi Finish Good Release and Finished Good Release as per marketing
authorization)
12. Quality Risk Management
13. Validation Program (Process Validation, Cleaning Validation and Analytical Method Validations)
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14. Qualification of equipment, instrument, water system and HVAC To support above quality elements various drug agencies have
issued few concept papers like (but not limited to following) :
1. Quality by Design (QbD) by CDER of USFDA
2. Process Analytical Technologies (PAT) by CDER of USFDA
3. Out of Specification (OOS) by CDER of USFDA
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4. Guidance for Automated System (21CFR part 11).

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REVIEW OF GOOD DISTRIBUTION PRACTICES:

Pharmaceutical Good Distribution Practice (GDP) is a vital component of Quality Assurance to ensure delivery of quality
products. It requires the pharmaceutical company to establish a quality system to ensure that products are consistently stored and
handled as required by the marketing authorization or product specification, thereby maintaining the quality of the products during
storage, transportation and distribution operations.
GDP is managed by supply chain personnel and the key result areas of personnel include prevention of counterfeit, spurious,
misbranded and adulterated product.

a. Health and Sciences Authority (HAS), Singapore :

Good Distribution Practice (GDP) certification is a voluntary scheme for interested companies seeking certification by
HSA attesting to its conformity with the standards described in HSA’s Guidance Notes of GDP, in relation to the storage and
distribution of medicinal products or active pharmaceutical ingredients.

b. PIC/S Guide to Good Distribution Practice:

Distribution and wholesalers must consider their ability to step up to the PIC/S level of compliance in light of the new
international requirements. Also significant consultation and brain storming with industry executives would be required, implying the
need for a long ‘lead time’ before local implementation is realistically expected.
i. Stringent controls for segregation/quarantine, equipment maintenance and calibration, and facility management
ii. Appropriate controls for computer systems, in line with current Good Manufacturing Practice (GMP) expectations
iii. Improved validation and calibration expectations
iv. All suppliers and customers must be qualified
v. Quality Risk Management (QRM) must be integrated throughout the Quality Management System (QMS)
vi. Internal quality audit is a process of Self Inspection
vii. Tighter controls associated with transportation, particularly for temperature sensitive medicines.
viii. Compliant management of all outsourced activities
ix. Documented contracts with all premises not controlled by the distributor

c. United States of Pharmacopeia (USP) Good Distribution Practices:

In the United States, Congress addressed supply system integrity with passage of the Prescription Drug Marketing Act in
1988. That legislation responded to the challenge of drug diversion in the wholesale distribution system and introduced the first
requirement for drug pedigrees to identify prior sales, purchases, or trades of drugs by anyone other than an authorized distributor of
record.
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d. EU Good Distribution Practices (GDP) Guideline:

It was published in 2013 in the Official Journal of the European Union is a very comprehensive form of guidance paper. The
European Union’s guidelines on Good Distribution Practice (GDP) were updated at the end of 2013
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GDP Chapter 1 – Quality Management

GDP Chapter 2 – Personnel
GDP Chapter 3 – Premises and Equipment
GDP Chapter 4 – Documentation
GDP Chapter 5 – Operations
GDP Chapter 6 – Complaints, returns, suspected falsified medicinal products and recalls
GDP Chapter 7 – Outsourced Activities
GDP Chapter 8 – Self-Inspections
GDP Chapter 9 – Transportation
GDP Chapter 10 – Specific Provisions for Brokers

GDP should be implemented through a quality system operated by the supply chain personnel and network of pharmaceutical
products to ensure that:
i. the medicinal products are authorized in accordance with law of land
ii. storage conditions are recorded at all times, including during transportation
iii. contamination from or of other products is prevented
iv. an adequate movement of stored pharmaceutical products takes place
v. products are stored in designated safe and secure area.

In addition to above, the quality system should ensure that the right products are delivered to the right customer within shelf
life period. A tracking system should facilitate any expired or defective products are found and there should be a procedure to respond
recall notification issued by manufacturing quality personnel.

Key Elements of GDP based on USP<1083>

RESULT OF COMPARISON: ‘GMP’ VIS-A-VIS ‘GDP’

The Good manufacturing practice (GMP) and good distribution practice (GDP) are considered related aspects of the quality
assurance. There is a connection between the two operations, GMP and GDP – to maintain product quality after a batch has been
released from the manufacturing site, as well as to illustrate and control complaints and a recall, if any. Sometimes it may appear that
GDP is smaller and less exhaustive than GMP, but this is not the case, as both have different arena and perspectives. There is much
less detail in GMP than can be found in GDP, if details of warehousing, storage and distribution operation is contemplated.
The drug regulatory agency plays an important role in coordinating these activities. The regulatory system for the supervision
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of pharmaceutical manufacturers and GMP inspection is one of the advanced quality system. Due to the globalisation of
pharmaceutical manufacture, it also affects the stakeholders including industry, regulators and patients .
Documentation of quality records is an important phenomena of GMP and GDP operations. The manufacturer should
maintain records of all manufacturing and distribution operations related to finished goods. All records should be maintained for
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defined retention period after the distribution. If expiration dating is used for a product, distribution records should be maintained at
least for one year past the expiry date of the product. Such records shall help a manufacturer to investigate market complaints or any
out of specification results of a marketed product.

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Vol 6, Issue 01, 2016. Nirmal Kumar et al. ISSN NO: 2231-6876

The pharmaceutical organizations will be inspected when they apply for a manufacturer or wholesaler dealer license and then
periodically granted approvals further based on risk assessments.
Good manufacturing practice (GMP) is the minimum standard that a medicines manufacturer comply to ensure that product must be:
 manufactured with consistently high quality
 appropriate to their intended use
 as per requirements of the marketing authorization (MA)
 conforming to the product specification

Good distribution practice (GDP) is more focused on supply chain management principle customized as per regulatory
obligation that requires that medicines are obtained from the
 licensed products are consistently stored, transported
 handled under suitable conditions, as required by the MA or product specification.

This study to compare the GMP and GDP operations illustrate a difference in approach with respect to quality system. The
GMP focuses on system related to manufacturing process, whereas GDP deals mainly with supply chain operations.

VALIDATION OF RESULTS:
The validation of the results is based on exploratory study. In order to validate the results of this study, the comments from
drug regulatory agencies were referred and compared.
 EU Guidance states that, the obvious difference between GDP and GMP is that GDP addresses the wholesale distribution of
pharmaceutical products, whereas GMP covers their manufacturing.
 In Europe the occurrence of shortages of medicines due to manufacturing and quality problems has increasingly reported over the
past few years.
 USP States that the goal of good distribution practices is to encourage sound business practices that help deter interference and
manipulation by bad actors and also to provide effective means to detect adulterated drug components and drug products to
prevent them from entering the supply chain.
Based on facts referred in comparative evaluation and opinion of drug regulatory agencies, it is observed that there is a gap
between quality perspectives during GMP and that during GDP.

CONCULSION
There is a gap in quality approaches of Good Manufacturing Practices (GMP) and Good Distribution Practices (GDP). The
pharmaceutical qualities have in depth focus during manufacturing operations which depend upon scientific tools, whereas quality is
perceived from business aspects. GMP is driven by pharmaceutical scientists, whereas GDP is led by supply chain managers. The
understanding of manufacturing managers and distribution managers about quality largely differ due to educational background of
personnel deployed in GMP and GDP. Hence there is a need of balanced approach by each pharmaceutical enterprise during
manufacturing and distribution operations. Neither of standards, GMP and GDP can alone ensure that quality product shall arrive to
customers.

RECOMMENDATION
In view of existing gap, a research is recommended to develop the model of integration between ‘Good Manufacturing
Practices and Good Distribution Practices’ to accomplish the organizational goal of quality system in pharmaceutical industry.
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ABBREVIATIONS:
ASEAN : Association of South-East Asia Nations
CFR : Code of Federal Regulations
CGMP : Current Good Manufacturing Practices
GDP : Good Distribution Practices
GMP : Good Manufacturing Practices
EMEA : European Medicines Agency
MA : Marketing Authorization
PIC/S : Pharmaceutical International Convention Scheme
QA : Quality Assurance
QRM : Quality Risk Management
QMS : Quality Management System
USFDA : United States Food and Drug Administration
USP : United States Pharmacopoeia
WHO : World Health Organization

CONFLICTS OF INTERESTS:
There is no conflict of interest involved in this article.

ACKNOWLEDGEMENT
A significant inspiration drawn for completing this review from Dr Ajoy Kumar Ray, Professor, Head of Department &
Dean, Sikkim Manipal Institute of Technology, Sikkim-India.

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REFERENCES
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2. GOV.UK, Comply with good manufacturing practice (GMP) and good distribution practice (GDP), and prepare for an inspection,
https://www.gov.uk/guidance/good-manufacturing-practice-and-good-distribution-practice, (Online Access Date-16-Dec-2015)
3. Dominic, The main differences between GDP and GMP, http://inspiredpharma.com/2014/11/12/the-main-differences-between-
gdp-and-gmp/ (Online Access Date-18 Dec-2015)
4. EudraLex - Volume 4 Good manufacturing practice (GMP) Guidelines, http://ec.europa.eu/health/documents/eudralex/vol-
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