Standards for Integrity Testing

Packaging integrity testing is a critical process for evaluating the reliability of pharmaceutical packaging. There are various methods of ensuring the packaging integrity, which help in protecting the pharma product and, at the same time, increase the efficiency of a pharma packaging. Among many factors, standards and regulatory body regulations are essential for ensuring the integrity of a pharma product packaging.

Every pharma manufacturer is legally and morally bound to adhere to regulatory regulations. These bodies' advantages are many, but mainly, without accrediting to these bodies, pharmaceuticals manufacturers are not allowed to enter any pharma market.

Advantages of Regulatory and Standardization Compliance

Compliance with standards and regulations is often termed a daunting task, which requires continuous process improvement, resourcefulness, and monitoring practices to troubleshoot any non-compliance issues. It also requires investment in the process, resources, and technical expertise to maintain regulatory compliance.

However, compliance with regulatory bodies is a worthwhile investment that pays off in both the short and long terms. Some advantages that compliance with regulatory bodies offers include, but are not limited to

Increased Customer Trust

Regulatory agencies and standardizing bodies have a strong research background, and their regulations are backed by thorough study, efforts, and experts. This makes their regulations proven in practical operations with guaranteed results. A manufacturer that adopts their regulations have access to the latest practices, and their workforce is more prepared for disaster management and mitigating risks common in day-to-day production. If their process or product fails, they have better arrangements and practices to tackle these issues.

The procedures mentioned above result in increased customer trust in the pharma manufacturer, which increases the customer market. Customers remain confident that they are getting the right value against their money spent, and more importantly, they remain hopeful that it will cure their diseases. Customer trust becomes more critical in the case of life-saving and biotech products, where the cost of the drug is significantly higher than ordinary pharmaceutical products.

Exposure to Latest technologies

Research and Innovation are common in the Regulatory and standardization bodies, the reason why they constantly update their regulations. The purpose of research is to deal with the latest challenges in the health sector and produce solutions that can be quickly and equally implemented across all the accredited industries.

Accrediting with these bodies gives access to the latest technologies that the regulatory bodies have invented by investing heavily in humans, processes, and products. Another advantage is the manufacturers do not have to spend as much as these bodies. Instead, they have only to follow their guidelines and gain access to the latest Innovation and technologies.

Easy access to regulated markets

Although there is a worldwide trend of making processes and products in a pharmaceutical industry compliant with regulatory bodies' guidelines, some markets, especially in third world countries, are still behind in achieving full regulatory status. However, first and second-world countries are highly regulated, and it is impossible to enter these markets without achieving total regulatory approvals.

The first and second world markets are profitable compared to third world countries. These markets give more value to a single dollar spent than other markets. Another advantage is that manufacturers that gain access to these markets are considered more credible. Their processes and products are more trusted than others. This also increases their business opportunities and profit margins compared to their competitors.

Regulations and Standardization for Packaging integrity testing

When acquiring compliance for pharma manufacturing, it is necessary for every process and product. Every pharma product process must be fully compliant, and if not, the manufacturer is not allowed to manufacture the product. The manufacturer can also face legal actions such as fines, product recalls, and even shut down of operations.

It is common in the pharmaceutical industry that one product or process is compliant while another product or process is not compliant. In that case, the product or process not compliant is not allowed for production until it is fully compliant with the regulations.

For the packaging integrity testing in the Pharmaceutical industry, the following are common regulations and standards.

USP 1207

The United States Pharmacopeia develops standards for products consumed by humans, including medicines. Pharma manufacturers and regulatory agencies use these standards to verify the processes and practices.

The USP 1207 guides are assuring the integrity of sterile packaging. According to USP 1207, integrity is defined as protecting the container’s constituents from leaking out and at the same time protecting it from outside harmful contaminants.

Following leaks are risky, and container should be able to deal specifically to these types

·       Microorganisms

It results in failure of product sterility

·       Leaking of headspace gas of a container

It includes loss of inert gasses from container or vacuum leak from a container. These gasses are often utilized to protect the product from getting reaction. It results in physicochemical failure of product.

·       Leaking of product from inside or allowing external liquid or solid to go inside

When this leak occur, the product is said to be physicochemical failed   

 Further guidance is provided in the following sub-sections of USP 1207.

·       USP 1207.1:  Package Integrity Testing in the Product Life Cycle—Test Method Selection and Validation

·       USP 1207.2:  Package Integrity Leak Test Technologies

·       USP 1207.3: Package Seal Quality Test Technologies

The standards outline in this guide apply to the following Small and large Volume Parenteral packages

·       Vials or bottles which are sealed with elastomeric closures or screw threaded caps

·       Form-Fill-Seal plastic or glass ampoules

·       Syringes or cartridges

·       Flexible bags or pouches

·       Packages for drug/device combination

ASTM F2338

ASTM International, formally known as the American Society for Testing and Materials, is an international standardization organization that develops standards for various materials and processes. Its membership is voluntary and is initiated by the organization itself, not by ASTM.

Vacuum Decay Test Method

The ASTM F2338 is a specialized test called Vacuum Decay Test. This test is based on the fact that if there is a leak in a packaged product, the vacuum decays or decreases, and pressure rises.

The vacuum is created in an enclosed container containing the package, by suitable apparatus. The vacuum is monitored for any decrease in its value. A small leak in pharma packaged product will change the vacuum value, monitored by these recording devices.

The apparatus contains transducers for measuring and recording the pressure value, which directly indicates the status of packaging integrity. It also contains mechanism for creating vacuum, possibly through a motorized mechanism. The motor creates vacuum, until desired value of vacuum is achieved. All the process executes automatically through the use of main controller, without human involvement.

Following types of packaging can be subject to vacuum decay test method

·       Plastic bottles with screw capped. This test can be applied container containg both Solids or Liquids

·       Glass or Plastic vials, containing Solids or Liquids

·       Glass or Plastic Ampoules

·       Glass Pre-Filled Syringes containing liquids or solids

·       Ophthalmic dropper tip bottles containing liquids

·       Blow Fill Seal bottle or strip containing liquid

·       Flexible and non-porous packaging such as pouches

·       Sealed cups or trays containing solids

Food and Drugs Administration – FDA

The Food and Drugs Administration in the United States is the agency for ensuring the quality and safety of pharmaceutical products and medicines. Every manufacturer that intends to manufacture or sell pharma products in the United States must comply with its regulations. If any pharma product is found without appropriate regulation status, the product is confiscated, and the manufacturer is fined for not acquitting the regulatory status.

The FDA regularly inspects and monitors pharma manufacturing facilities to check whether they are complying with the regulations.

In the United States, every federal agency is represented by the Code of Federal Register – CFR, followed by its specific number. The FDA has a CFR number of 21. Every time a CFR has a number 21 attached, it represents Food and Drug Administration regulations. The FDA has regulations and guidelines for each process in a pharma environment, including the packaging processes.

Regulations for packaging integrity are mentioned in part 211 of 21CFR and are called Current Good Manufacturing Practices. Its section 94 contains guidelines for packaging integrity for finished pharma products. There are three variants of these regulations concerning packaging integrity testing, indicated by a,b and c. These are indicated as follows

21CFR211.94(a)

According to this regulation “ Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug beyond the official or established requirements.”

21CFR211.94(b)

According to this regulation “Container closure systems shall provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product”.

21CFR211.94(c)

According to this regulation “Drug product containers and closures shall be clean and, where indicated by the nature of the drug, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use. Such dehydrogenation processes shall be validated”.

21CFR211.94(d)

According to this regulation “Standards or specifications, methods of testing, and, where indicated, methods of cleaning, sterilizing, and processing to remove pyrogenic properties shall be written and followed for drug product containers and closures.”

About the Author：

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.