Sterilization of Medicinal Products Guidelines

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Questions and Answers

What are the two committees responsible for the publication of this guideline?

The Committee for Medicinal Products for Human use (CHMP) and the Committee for Medicinal Products for Veterinary use (CVMP)

What is the name of the document that this guideline replaces?

Decision trees for the selection of sterilisation methods

When did the public consultation period for this guideline begin and end?

The public consultation period started on 13 April 2016 and ended on 13 October 2016.

Which groups agreed on this guideline in the year 2018?

The BWP, CAT, QWP, and GMDP IWG all agreed on this guideline in 2018. Signup and view all the answers

What was the date on which this guideline officially came into effect?

The guideline came into effect on 1 October 2019. Signup and view all the answers

What is the official address of the EMA?

Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands Signup and view all the answers

How can individuals contact the European Medicines Agency with inquiries?

Individuals can submit questions via the website, <a href="http://www.ema.europa.eu/contact">www.ema.europa.eu/contact</a>, or by calling +31 (0)88 781 6000. Signup and view all the answers

What is the copyright year for this document?

2019 Signup and view all the answers

What specific guidelines should be followed for Advanced Therapy Medicinal Products (ATMPs)?

The Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products should be followed. Signup and view all the answers

Why is it important to describe the packaging process when a secondary container is used?

It is crucial as it may affect the sterility of the finished product, especially regarding moisture trapping between containers. Signup and view all the answers

What documentation is required for the sterilization and aseptic processing of medicinal products?

Documentation must be provided for all sites performing sterilization or aseptic processing, whether in-house or outsourced. Signup and view all the answers

What factors should be justified regarding sterilization if a secondary container is used?

The justification should relate to sterility assurance and any potential impact on finished product quality. Signup and view all the answers

What needs to be included in the quality dossier concerning filters used in manufacturing?

A description of all filters that come in contact with the finished product or its components must be provided. Signup and view all the answers

How should the timing of the packaging step relative to sterilization be documented?

Information should be provided indicating whether the packaging step is performed before or after sterilization. Signup and view all the answers

What is the minimum lethality requirement for steam sterilisation processes according to the content?

The minimum lethality requirement is F0 ≥ 8 minutes. Signup and view all the answers

What temperature is required for the minimum process hold during steam sterilisation?

The minimum process hold temperature required is 110 °C. Signup and view all the answers

What sections contain specific documentation for human products regarding sterilization?

Documentation is found in sections such as 3.2.S.2 Manufacture, 3.2.P.2 Pharmaceutical development, and others. Signup and view all the answers

What is the potential risk associated with moisture trapping between primary and secondary containers?

The potential risk is contamination or loss of sterility of the finished product. Signup and view all the answers

When is validation data for the sterilisation cycle not required in the quality dossier?

Validation data is not required when using the reference condition of Ph.Eur. 5.1.1 (≥121 °C, ≥15 min). Signup and view all the answers

What does a SAL of 10-6 indicate about sterilised items?

It indicates that there is a probability of not more than 1 non-sterile item in 1 × 10^6 sterilised items. Signup and view all the answers

What must be justified if steam sterilisation is performed with a finished product temperature below 115 °C?

It must be scientifically justified and supported by additional data. Signup and view all the answers

What are the slowest to heat locations during sterilisation?

They are the locations in the load that remain coldest or where the temperature is increasing the slowest. Signup and view all the answers

In the context of steam sterilisation, what does the F0 concept relate to?

The F0 concept relates to the lethality and microbial reduction during the steam sterilisation process. Signup and view all the answers

How is steam sterilisation defined in the context provided?

It refers to a sterilisation process that employs steam as described in Ph.Eur. 5.1.1. Signup and view all the answers

What is the acceptable bioburden limit for aqueous solutions according to the content?

The acceptable bioburden limit is in line with any pre-sterilisation bioburden reduction process capability. Signup and view all the answers

What is required for a process to be considered effective sterilisation?

It must be suitably designed, validated, and controlled to inactivate or remove viable microorganisms. Signup and view all the answers

What should be justified if temperatures below 110 °C are included in the determination of F0?

This inclusion should be justified. Signup and view all the answers

Under what circumstances may moist heat processes with an F0 < 8 min be suitable?

They may be suitable as a post-aseptic processing terminal heat treatment for certain formulations. Signup and view all the answers

What does sterility mean in the context of sterilisation?

Sterility is defined as the absence of viable microorganisms. Signup and view all the answers

What is the significance of a sterility assurance level?

It signifies the confidence level in the sterilisation process to produce sterile products. Signup and view all the answers

Can the concept of slowest to heat locations apply to other sterilisation methods?

Yes, it can be used figuratively for any sterilisation method to identify locations with the lowest level of sterilising energy. Signup and view all the answers

What is the maximum level of viable microorganisms allowed for a product to be considered sterile with SAL 10-6?

The level of viable microorganisms must be equal to or less than 10^-6. Signup and view all the answers

What factors should be considered when determining the Sterility Assurance Level (SAL)?

The maximum bioburden per container and the D-value of the biological indicator used in validation should be considered. Signup and view all the answers

How is the D121-value related to the SAL in low energy steam processes?

A bio-indicator with a D121-value of at least 12 minutes is used to validate processes requiring at least a 12 log reduction. Signup and view all the answers

What are the reference conditions for sterilization as specified in Ph.Eur. 5.1.1?

The reference conditions include terminal steam sterilization at ≥121 °C for 15 min, dry heat at ≥160 °C for ≥2 h, or ionizing radiation of 25 kGy. Signup and view all the answers

What is the significance of providing additional validation data in the quality dossier?

Additional validation data is crucial for low energy steam processes to corroborate the effectiveness of the sterilization method. Signup and view all the answers

Explain the concept of Sterility Assurance Level (SAL).

SAL expresses the probability of micro-organisms surviving in a product item after exposure to the sterilization process. Signup and view all the answers

What constitutes a terminal moist heat process in post-aseptic processing?

It is employed after aseptic processing and aims to achieve a SAL ≤10-6 without fulfilling specific steam sterilization requirements. Signup and view all the answers

What process parameters must be met for a sterilization cycle to be validated?

A process must show at least a 12 log reduction of biological indicator micro-organisms with a minimum D value of 1 minute. Signup and view all the answers

What is intended by stating the terminal steam sterilization process at ≥121 °C for 15 min?

It denotes the specific conditions required for effective sterilization to achieve the desired SAL. Signup and view all the answers

What is the primary method of ensuring sterility for medicinal products, according to the EMA/CHMP/CVMP/QWP/850374/2015 guideline?

Terminal sterilization using a reference condition of the European Pharmacopoeia (Ph.Eur.) is the preferred method whenever possible. Signup and view all the answers

Why does terminal sterilization using the European Pharmacopoeia reference condition hold a position of preference in the context of sterility assurance?

Terminal sterilization using the European Pharmacopoeia reference condition is preferred because it is lethal to microorganisms and allows for reliable calculation, validation, and control of the sterility assurance level (SAL), thus incorporating a safety margin. Signup and view all the answers

What alternative methods, besides terminal sterilization, may be used to ensure sterility for medicinal products, according to this guideline?

Alternative methods include sterilising filtration, aseptic processing, or a combination of aseptic processing with an additional post-aseptic processing terminal heat treatment. Signup and view all the answers

What specific documentation is recommended for sterile finished products, active substances, excipients, and primary containers in a "quality dossier" for a new marketing authorization or variation application?

The documentation expected for sterile finished products, active substances, sterile excipients, and sterile primary containers (containers) should be included in the quality dossier. Signup and view all the answers

What is the critical quality attribute for all sterile substances, products, and containers, according to this guideline?

Sterility is the critical quality attribute for all sterile substances, products, and containers. Signup and view all the answers

How can sterility be achieved for medicinal products, according to this guideline?

Sterility is achieved by controlling several factors, including the bioburden, the sterilization procedure, the integrity of the container closure system, and the use of satisfactory aseptic technique, particularly in the case of aseptic processing. Signup and view all the answers

Why is terminal sterilization considered a more preferred method compared to sterilising filtration and aseptic processing?

Terminal sterilization is preferred because it directly eliminates microorganisms, enabling the reliable calculation, validation, and control of the sterility assurance level (SAL), thus incorporating a safety margin. Signup and view all the answers

What key factors are highlighted as contributing to the overall control and assurance of sterility in the manufacturing process?

Key factors include controlling the bioburden, the sterilization procedure, the integrity of the container closure system, and ensuring satisfactory aseptic technique in the case of aseptic processing. Signup and view all the answers

Flashcards

CHMP

Committee for Medicinal Products for Human use; evaluates human medicines in the EU.

CVMP

Committee for Medicinal Products for Veterinary use; evaluates veterinary medicines in the EU.