On this page: Sampling and testing of starting materials used in sunscreen manufacture | Sampling and testing of finished sunscreen product | Validation of test methods | Conducting ongoing stability studies
Sampling and testing of starting materials used in sunscreen manufacture
Quality Control is concerned with sampling and testing of all materials used throughout the manufacturing process to established specifications, including starting materials, intermediates, excipients, preservatives, sunscreen agents and final bulks or products, to ensure quality before release for further processing or supply.
Standards applicable to starting materials used in sunscreen manufacture
You must demonstrate an active ingredient or an excipient meets the requirements of the default standard, if an applicable monograph exists (Part 3-1: standards, Therapeutic Goods Act 1989), unless we have given the sponsor consent for the goods not to comply with that standard.
See the tables below for guidance on current TGA expectations for minimum sampling and testing of sunscreen agents, excipients and preservatives.
For more detail on supplier qualification see Supplier assessment, approval and qualification for listed and complementary medicines, which can also be applied to sunscreens.
| Criteria - Pre Qualification | Criteria - Post Qualification | |
|---|---|---|
| Sampling | All containers to be sampled. | √n + 1, or reduced sampling plan based on risk assessment. Manufacturer to justify. |
| Testing |
As per EP/BP/USP monograph, or to an established specification if no monograph is applicable.
|
Established specification
|
| Criteria - Pre Qualification | Criteria - Post Qualification | |
|---|---|---|
| Sampling |
√n + 1 (where n = number of containers received) |
1 sample per delivery |
| Testing |
As per EP/BP/USP monograph, or to an established specification if no monograph is applicable.
|
Established specification.
|
Sampling and testing of finished sunscreen product
Bulk & finished product: minimum sampling
We expect:
- sampling plans to be documented
- consideration to be given to sampling of bulk product from formulation tanks prior to packaging
- where testing occurs on the finished pack for release purposes, samples to be taken throughout the packaging run and be representative of the entire batch.
Bulk & finished product: testing
Sufficient testing, including active ingredient assay, should be conducted to verify the quality of the product. For multi active products, reduced and/or rotational testing may be implemented where justified.
Chemical testing can occur on either the bulk or packed product provided studies are available to demonstrate the bulk product remains homogeneous across the bulk product's storage period, and throughout the filling process. Special consideration for additional sampling and testing may need to be given to products that do not remain in a homogenous state e.g. suspension products.
There is normally no need for repeat chemical testing of the packed product if it is already performed on the bulk product.
Microbiological testing on the finished packed product should normally be conducted prior to release. Sunscreen products must comply, throughout the shelf life, with the microbiological requirements outlined in Therapeutic Goods Order No. 100 Microbiological Standards for Medicines. The frequency of microbiological testing should be justified based on the following:
- the normal expected microbial quality of starting materials, including water quality
- the manufacturing processes employed, and their ability to control/reduce microbial contamination
- product formulation including the water content of the product and the effectiveness of any preservative system
- historical microbiological test results for the product
- risk to patient safety
Validation of test methods
Validate and/or verify all microbiological methods used in the testing of starting materials and finished products for the material under test. Evidence of these studies should be recorded.
Using analytical methods included in BP, EP or USP
Analytical methods for starting materials do not require additional validation where the pharmacopoeial method is employed.
Analytical pharmacopoeial methods for finished formulations do need validation to determine any effects from the formulation process. All analytical method validations should be recorded.
Using analytical methods not included in BP, EP or USP
All methods not listed in a relevant pharmacopeia should be validated for testing of starting materials or product formulations.
For guidance on the characteristics for consideration during the validation of analytical procedures, see:
- CPMP/ICH/381/95: ICH Topic Q 2(R1) - Note for Guidance on Validation of Analytical Procedures: Text and Methodology
Conducting ongoing stability studies
Responsibility for the ongoing stability program
Stability testing for sunscreens is mandatory. All responsibilities related to ongoing stability testing should be defined in a GMP agreement (unless the sponsor, manufacturer and authorised person conducting release for supply are all from the same entity).
- ensure that there is stability data to support the shelf life of the product
- have access to the laboratory results
The individuals conducting release for supply need to:
- have adequate information to support the shelf life of the product being released
- have adequate information to confirm that the batch meets the requirements for marketing authorisation
The stability testing program can be contracted out to third parties. This can include physical storage under the specified controlled conditions and undertaking the testing at the specified time points.
Development of stability protocol
Conduct the initial stability study in accordance with a predetermined protocol, which should be in line with the ICH Guideline time points for stability testing outlined in CPMP/ICH/2736/99: ICH guideline is ICH Topic Q 1 A (R2) - Note for Guidance on Stability Testing: Stability Testing of New Drug Substances and Products. Ongoing stability studies may use different time points as the data is used to confirm that the product remains stable over its shelf life when the initial studies have already been confirmed as acceptable.
Include in the protocol relevant physical, chemical and microbiological testing to support the marketed shelf life of the product. The protocol for an ongoing stability program should extend to at least the end of the shelf life period.
Stability conditions
Stability testing for sunscreens should be conducted in real time at the storage conditions specified on the product label. For example:
- 30 °C ± 2 °C when the label storage conditions are ‘store below 30 °C' or ‘store at room temperature'
- 25 °C ± 2 °C when the label storage conditions are ‘store below 25 °C'
Humidity control is not required for on-going stability studies of sunscreen products.
Accelerated stability studies in the ongoing stability program
Accelerated stability studies are not required for post market ongoing stability studies.
Method development and validation
Analytical methods are researched, developed and validated for a product or group of products. The methods used for the stability testing of products need to be stability-indicating.
As a minimum, validate methods for specificity and robustness in accordance with the TGA’s Finished product (medicine) analytical procedure validation for complementary medicines.
It is unnecessary to monitor the level of impurities for sunscreen products.
GMP certified laboratory or facility for on-going stability studies
Storage of ongoing stability samples and the associated testing do not need to be conducted in a GMP certified laboratory or facility, because ongoing stability testing is not considered to be a step in manufacture, as defined by the Therapeutic Goods Act 1989.
However, the results from these studies are required to be reliable and meaningful. It is the responsibility of the contract giver to ensure that any facilities or laboratories used for ongoing stability testing is appropriate. For that reason, other certification may be used in lieu of GMP certification, such as a licence issued by a regulatory authority acceptable to TGA or a current ISO 17025 accreditation certificate.
The results from the on-going stability monitoring studies must be considered as part of release for supply, which is the final step in manufacturing.
Types of product
Ongoing stability testing is of the finished packed product.
Consider whether bulk product should also be part of the ongoing stability program, particularly where bulk product is stored prior to being packaged or transported from a manufacturing site to a packaging site. To determine whether further studies are necessary, use a risk assessment process to evaluate the impact of storage of bulk products on the stability of the packaged product.
In general, further studies may be appropriate if storage is more than one month for bulk sunscreen products.
Types of testing
Physical testing parameters
Include physical testing parameters specific to the sunscreen product, including pack integrity.
Microbiological testing
Consider microbiological testing throughout the study to support compliance with the expiry specifications. At a minimum, conduct microbiological testing at the initial and the end time points of the study.
Sunscreen agents
Test the active ingredients that are claimed on the label throughout the study using validated stability-indicating methods.
Reduced ongoing stability testing may be acceptable, with a documented risk assessment and justification, if full stability data for the support of the product listing shelf life is available for all active ingredients as per the label claim.
Grouping for the purposes of stability testing
A grouping approach can be undertaken with stability studies in recognition of the similarity of many sunscreen products. Scientific justification of the rationale to establish product groupings should be documented.
Justifications should be based on groupings for products having similar formulations and with a similar method of manufacture. The groupings used for the preparation of PQRs would generally be acceptable for sunscreen products. The packaging of the product should also be taken into consideration.
An on-going stability program commences when a batch of product within a group is placed on stability, provided that the justification is documented for this particular product being representative of the grouping. Rotating of products within a group would also be acceptable.
At least one batch of product from each group each year should be placed on the ongoing stability program under the predetermined study protocol.
Release for supply and ongoing stability program results
The results of the ongoing stability program are expected to be available to the authorised person who should consider the results before releasing a batch for supply.
Ongoing stability study reports
Ongoing stability study reports should be available to:
- the authorised person responsible for release for supply
- the sponsor
- the TGA for review when requested
Ongoing stability reports should be summarised and authorised by a suitably experienced and qualified individual with a quality and/or technical and/or regulatory background for inclusion in the Product Quality Review.
The operation of an appropriate ongoing stability program including the results of ongoing stability studies, are normally reviewed during GMP inspections. If there are any concerns, the inspector can refer the evaluation to the area of TGA responsible for regulating the product ARTG entry.
Notifying TGA of ongoing stability issues
All significant departures from established stability profiles must be notified to the TGA. It is acknowledged that some normal variability in the results of ongoing stability studies can be expected.
In general, if an assessment of stability data highlights that there is a likelihood that new batches may not stay within their label claim for the duration of a sunscreen product’s shelf life, then the manufacturer or sponsor should notify TGA.
A departure from physical quality attributes, such as phase separation, is also significant and should be reported to TGA.