Manufacturing Pharmacy Laboratory

Research Output;

GMP, GDP, GSP, & GLP

Submitted By:

WAHEED B. KAREEM

Submitted To:

MA. VICTORIA E. MENDOZA, RPh MS Ph

Date Submitted:

November 23, 2017.

 Description of Current Good Manufacturing Practices (cGMP)

Good Manufacturing Practice (GMP) is a method for ensuring that products are consistently
produced and controlled according to quality standards. It is designed to minimize the risks involved in
any pharmaceutical production that cannot be eliminated through testing the final product.

GMP refers to the Good Manufacturing Practice and it sometimes referred to as "cGMP". The
"c" stands for "current," reminding manufacturers that they must employ technologies and systems
which are up-to-date in order to comply with the regulation. Regulations promulgated by the US Food
and Drug Administration (FDA) under the authority of the Federal Food, Drug, and Cosmetic Act. These
regulations, which have the force of law, require that manufacturers, processors, and packagers of
drugs, medical devices, some food, and blood take proactive steps to ensure that their products are
safe, pure, and effective.

GMP covers all aspects of manufacturing from the starting materials, premises, and equipment
to the training and personal hygiene of staff. Detailed, written procedures are essential for each process
that could affect the quality of the finished product. There must be systems to provide documented
proof that correct procedures are consistently followed at each step in the manufacturing process -
every time a product is made.

GMP REGULATIONS AND PREAMBLES

Administrative Order No. 220 s. 1974.

(Drugs: Current Good Manufacturing Practice in Manufacture, Processing, Packaging or Holding)

Definitions- the definitions and interpretations contained in section 10 of the Food, Drug and Cosmetics
Act RA 3720 are applicable to such terms when used in this regulation. The following definitions shall
also apply:

a) “Component” (raw material) means any ingredient intended for use in the manufacturing of drugs,
including those that may not appear in the finished product.

b) “Batch” means a specific homogenous quantity of a drug or in case of drug produced according to
single manufacturing order during the same cycle of manufacture.

c) “Lot” means a batch or any portion of batch of a drug produced by a continuous process, an amount
of drug produced in a unit of time or quantity in a matter that assures its uniformity and in either case
which is identified by a distinctive lot number and has uniform character and quality within specified
limits.

d) “Lot number” or “control number” means any distinctive combination of letters or numbers, both, by
which the complete history of the manufacture, control, packaging and distribution of a batch or lot of a
drug is determined.
e) “Active ingredient” means any substance of a which is intended to furnish pharmacological activity or
other effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the
structure or any function of the body of man or other animals.

f) “Inactive ingredient” means any substance other than “active ingredient” present in a drug.

g) “Materials approval unit” means an organizational element having the authority and responsibility to
approve or reject raw materials, in-process materials, packaging components, and final products.

h) “Strength” means:

(I) the concentration of known active drug substance in formulation (for example, w/w, w/v, or
unit dose /volume basis).

(II) potency, that is, the specific ability or capacity of the product as indicated by appropriate
laboratory tests or by adequately controlled clinical data obtained through the administration of the
product in the manner intended to effect a given result (s) expressed, for example, in terms of units by
reference to a standard).

Why GMP is important?

 A poor quality medicine may contains toxic substances that have been unintentionally added.
 A medicine that contains little or none of the claimed ingredient will not have the intended
therapeutic effect.

How does FDA determine if a company is complying with CGMP regulations?

FDA inspects pharmaceutical manufacturing facilities worldwide, including facilities that

manufacture active ingredients and the finished product. Inspections follow a standard approach and
are conducted by highly trained FDA staff. FDA also relies upon reports of potentially defective drug
products from the public and the industry. FDA will often use these reports to identify sites for which an
inspection or investigation is needed. Most companies that are inspected are found to be fully compliant
with the CGMP regulations.

cGMP For Finished Pharmaceuticals

1. General Provision; This section states that the company’s adherence to the requirements of the
entry set of regulation determined whether its output will be judged as adulterated or violative.
2. Organization & Personnel; this deals with Responsibilities of quality control unit
personnel qualifications, and personnel responsibilities
3. Buildings and Facilities; any building or buildings used in the manufacture, processing, packing or
holding of drug product shall be of suitable size, construction and location to facilitate cleaning,
maintenance, and proper operations. Regarding buildings and facilities, there are two major
areas of concern: the external environment and the internal environment.
 4. Equipment; Equipment used in the manufacture, processing, packing, or holding of a drug
product shall be of appropriate design, adequate size, and suitably located to facilitate
operations for its intended use and for its cleaning and maintenance.
5. Control of Components and Drug Product Containers and Closures; are procedures describing in
sufficient detail the receipt, identification, storage, handling, sampling, testing and approval or
rejection of components and drug product containers and closures; such written procedures
shall be followed.
6. Production & Process Control
7. Packaging and Labeling Control
8. Handling & Distribution; dealing with warehousing procedures with distribution of the
pharmaceuticals.
9. Laboratory Control
10. Records Reports
11. Returned & Salvaged Drugs.

Description of Good Distribution Practice (GDP)

Good distribution practice (GDP) deals with the guidelines for the proper distribution of medicinal
products for human use. GDP is a quality warranty system, which includes requirements for purchase,
receiving, storage and export of drugs intended for human consumption.

GDP regulates the division and movement of pharmaceutical products from the premises of the
manufacturer of medicinal products, or another central point, to the end user thereof, or to an
intermediate point by means of various transport methods, via various storage and/or health
establishments.

When the distribution chain is interrupted by manufacturing steps such as repackaging and relabeling,
the principles of good manufacturing practices (GMP) should be applied to these processes. Counterfeit
pharmaceutical products are a real threat to public health and safety. Consequently, it is essential to
protect the pharmaceutical supply chain against the penetration of such products. Weak points in the
distribution processes of pharmaceutical products provide an avenue for counterfeit as well as illegally
imported, stolen and substandard medicines to enter the supply chain.

General principles of Good Distribution Practice (GDP)

a. All parties involved in the distribution of pharmaceutical products have a responsibility to

ensure that the quality of pharmaceutical products and the integrity of the distribution chain is
maintained throughout the distribution process from the site of the manufacturer to the entity
responsible for dispensing or providing the product to the patient or his or her agent.
b. The principles of GDP should be included in national legislation and guidelines for the
distribution of pharmaceutical products.
 c. The principles of GDP are applicable both to pharmaceutical products moving forward in the
distribution chain from the manufacturer to the entity responsible for dispensing or providing
pharmaceutical products to the patient
d. All entities involved in the distribution process should apply due diligence with adherence to the
principles of GDP
e. There should be collaboration between all parties including governments, customs agencies, law
enforcement agencies, regulatory authorities, manufacturers, distributors and entities
responsible for the supply of pharmaceutical products to patients to ensure the quality and
safety of pharmaceutical products.

Description of Good Laboratory Practices (GLP)

Good Laboratory Practice is defined in the OECD Principles as “a quality system concerned with
the organizational process and the conditions under which non-clinical health and environmental safety
studies are planned, performed, monitored, recorded, archived and reported.”
The purpose of the Principles of Good Laboratory Practice is to promote the development of
quality test data and provide a tool to ensure a sound approach to the management of laboratory
studies, including conduct, reporting and archiving. The Principles may be considered as a set of
standards for ensuring the quality, reliability and integrity of studies, the reporting of verifiable
conclusions and the traceability of data.
The Principles require institutions to assign roles and responsibilities to staff in order to ensure
good operational management of each study and to focus on those aspects of study execution
(planning, monitoring, recording, reporting, archiving) that are of special importance for the
reconstruction of the whole study.
A quality system concerned with the organizational process and the conditions under which
non-clinical Health and environmental safety studies are planned, performed, monitored, recorded,
archived and reported. GLPs are regulations published in the Code of Federal Regulations, These are not
guidelines, and they have the force of law and are not “watered down”

FDA GLP Regulations Apply to (58.1)

• Non-clinical laboratory studies that support or are intended to support application for research or
marketing permits for the following products:

– food and color additives

– human and animal drugs
– medical devices for human use
– biological products
– electronic products

• GLPs have nothing to do with manufacturing product!

 Basic Elements of GLP

1. Personnel
Sponsor

- Management

Quality Assurance

Study Director
2. Documents

Protocols

Standard Operating

Archiving

Reports

3. Facility

Characterization

Reagents

Storage

Laboratory Operation

Animal care

4. Test and Control Articles

Equipment

Handling

Storage

Conclusion

There is no such thing as GLP lots, and GLPs do not apply to manufacturing anything. Product
manufactured for toxicology studies must be tested for safety. These in vitro and in vivo tests must be
conducted in compliance with GLPs and clinical material must be tested for safety and efficacy in
humans. These tests in humans must abide by GCPs

Description of Good Storage Practices (GSP)

Good Storage practices are that part of the quality assurance that ensures that the quality of a
pharmaceutical product is maintained through adequate control throughout the storage. Storage forms
an important activity of the integrated supply chain management of the pharmaceutical products
(Medicine).

The Storage & distribution of Pharmaceutical products are activities that are carried out by
various companies, institutions and individuals. The nature of the risks involved may generally; however
be the same as those in the manufacturing environment, e.g. mix-ups, contamination and cross –
contamination.

What does this means?

 Keep in a cool, dry place: keep it in a place away from direct sources of heat or sunlight, in a
closed cabinet.
 Keep in a cold place: Keep it in the refrigerator compartment (Not in the Freezer), Remember
that if a medication is not stored properly, it may lose its potency earlier than the expiry date
mentioned on the pack.

Do note store the Medications:

 In bathroom cabinets, as the air over there is humid and it is hotter.

 In the kitchen, as this place is hotter & humid compared to other places in the house
 Close to windows or in the balcony, as these places are hotter, directly expose the medicines to
sunlight, compared to other places in the house.

Storage and labelling conditions

Normal storage conditions

Storage in dry, well-ventilated premises at temperatures of 15 –25°C or, depending on climatic

conditions, up to 30°C. Extraneous odors, other indications of contamination, and intense light must be
excluded.

Defined storage instructions

Drug products that must be stored under defined conditions require appropriate storage
instructions. Unless otherwise specifically stated (e.g. continuous maintenance of cold storage)
deviation may be tolerated only during short-term interruptions, for example, during local
transportation.

The use of the following labelling instructions are recommended:

On the label Means

“Do not store over 30°C” from +2°C to +30°C

“Do not store over 25°C” from +2°C to +25°C

“Do not store over 15°C” from +2°C to +15°C

“Do not store over 8°C” from +2°C to +8°C

“Do not store below 8°C” from +8°C to +25°C

“Protect from moisture” no more than 60% relative humidity in normal storage
conditions; to be provided to the patient in a moisture-resistant
container.

“Protect from light” to be provided to the patient in a light-resistant container.

References:
 http://www.who.int/medicines/areas/quality_safety/quality_assurance/TRS986annex2.pdf?ua1
 https://ispe.org/initiatives/regulatory-resources/gmp/what-is-gmp
 http://www.fda.gov.ph/attachments/article/19472/ao%20220%20s%201974.pdf
 https://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm169105.htm
 http://www.pharmatips.in/Articles/Quality-Assurance/GMP/Finished-Pharmaceutical-General-
Provision.aspx
 http://www.pharmatips.in/Articles/Quality-Assurance/GMP/Finished-Pharmaceutical-General-
Provision.aspx
 https://en.wikipedia.org/wiki/Good_distribution_practice
 http://apps.who.int/medicinedocs/documents/s18675en/s18675en.pdf