2019

EXPERT ANSWERS

Pharmaceutical standards

Q: Are there World Health Organization (WHO) current good manufacturing practices (cGMP) for manufacturing liquid and semisolid dosage forms? If not, what is the equivalent alternative?

Muhammad Mostafa
Abusultan, Ismailia, Egypt

A: WHO has issued numerous standards, including a standard for cGMPs for pharmaceutical manufacturers. The first draft of the cGMP standard was issued in 1968. It has been updated many times, and the most recent version was released this year.

cGMP is just one element of the WHO certification scheme to ensure the quality of pharmaceutical products via international trade. The standard is used to justify cGMP status, and may be used as a basis for inspection of manufacturing facilities and as a training guide for inspectors and quality assurance personnel.

WHO does not have the authority to enforce the standard, but importing countries can require compliance with the standard as part of their purchasing agreement with the exporting company. This is particularly beneficial for developing nations that do not have the resources or experience to develop their own regulations.

The WHO cGMP standard is quite comprehensive and is nearly 60 pages long. cGMP ensures that medicines are consistently produced and adequately controlled throughout the manufacturing and distribution process. The intent is to minimize the risks associated with manufacturing to ensure the safety, purity and efficacy of the product.

Most medicines also must comply with the International Pharmacopoeia. This document lists thousands of product specifications and monographs for specific medicines and describes various laboratory procedures to test the medicines.

The recent updates to the WHO cGMP standard include new requirements for process validation, annual product reviews and risk management. Other requirements cover sanitation of equipment and facilities, control of raw materials and packaging, calibration of equipment, training of personnel, documentation, investigations, internal audits, complaint processing and other topics.

In many ways, the WHO standard is similar to the U.S. Food and Drug Administration’s (FDA) 21 Code of Federal Regulations Part 211 for pharmaceuticals. I have not compared the standards in detail, but the members of the WHO expert committee regularly review the FDA and European standards and update the WHO standard as needed.

The WHO standard is generic in that it applies to manufacturing practices and supporting quality management systems, regardless of the medicine being manufactured.

For example, paragraph 16.4 states, "Checks on yields and reconciliation of quantities should be carried out as necessary to ensure that there are no discrepancies outside acceptable limits."1 It does not specify a minimum acceptable yield.

In addition, the word "should" can be interpreted as "a strong recommendation." Therefore, to be in compliance, batch records "should" include some sort of material reconciliation. These practices apply whether the manufacturer is making oral liquids, pills, eye drops or injectable drugs.

It is quite possible that liquid and semisolid dosages are covered in one or more of the U.S., European or International Pharmacopoeia standards. The WHO cGMP standard complements the International Pharmacopoeia standards. Depending on the country involved, you must comply with the WHO cGMP standard and the International Pharmacopoeia standards. Perhaps the best advice I can give you is to consider the regulations of all the countries where you want to do business and adopt the most stringent standards.

The WHO cGMP standard is available for free in electronic form at www.who.int. In the search box, type "TRS 986" in quotation marks. The title of the standard is WHO Expert Committee on Specifications for Pharmaceutical Preparations.

Andy Barnett
Director, quality systems
NSF International
Houston

Reference

  1. World Health Organization, WHO Expert Committee on Specifications for Pharmaceutical Preparations, paragraph 16.4, June 2014.
     

Clarifying ISO notes

Q: Can I use an ISO contamination note on a drawing if the organization isn’t ISO 9001 certified? The contamination note I am referring to reads: "Each tube assembly shall be cleaned to an ISO solid contamination code of 17/14." I realize this is a note for the range of particulates. I was curious if I could add ISO notes to a drawing if our organization is not ISO 9001 certified.

Michael Benishek
Clintonville, WI

A: Table 1 shows the ISO 4406:1999 contamination codes presented as 19/17/14 or 21/19/16.1 Each number represents a contaminant level code for the correlating particulate size.2

Table 1

ISO 9001 is a management systems standard, and the ISO contaminant codes explained in Table 1 are a product specification (cleanliness of fluid). There are several products and process-specific ISO standards used in the drawings as a requirement for manufacturing, procurement or subcontracting services. Irrespective of whether an organization is ISO 9001 certified, it is important to specify appropriate standards to ensure product and process quality.

There is no restriction to put this requirement (relevant ISO standards) in the drawing if you are not ISO 9001 certified. However, if you are ISO 9001 certified, you should include applicable requirements. This is addressed in ISO 9001:2008, Clause 7.3.2—Design and development inputs, which states "product requirements shall be determined."3 These inputs shall include "functional and performance requirements, applicable statutory and regulatory requirements, other requirements essential for design and development."4

Similarly, Clause 7.4.2—Purchasing information describes the product to be purchased, including, where appropriate, requirements for approval of product, procedures, processes and equipment.5

Typical examples of inclusions of such standards are drawings requiring welding quality, mechanical testing and surface quality requirements.

Govind Ramu
Director, quality assurance
SunPower Corp.
San Jose, CA

References

  1. Velcon Filters, "ISO Fluid Cleanliness," 2011,
  2. Precision Filtration Products, "Understanding ISO Codes,"
  3. International Organization for Standardization, ISO 9001:2008—Quality management systems—Requirements, Clause 7.3.2—Design and development inputs.
  4. Ibid.
  5. International Organization for Standardization, ISO 9001:2008—Quality management systems—Requirements, Clause 7.4.2—Purchasing information.

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