According to the European regulation for cosmetics (EU Reg. n° 1223/2009) the responsible person who places cosmetic products on the European market must be able to demonstrate that such products are safe for human health, under normal conditions of use or reasonably foreseeable, in order to always guarantee maximum consumer protection.
In order for the responsible person to fulfill this obligation, they must draw up, or have it drawn up on their behalf, the Product Information File (PIF), i.e. the mandatory information documentation on the cosmetic product placed on the market.
The PIF must be kept by the responsible person for at least 10 years after the date on which the last batch of the product was distributed on the market. Furthermore, the PIF must be kept up to date and in immediate disposition of the authorities by the responsible person.
What information must be contained in the PIF?
The European Regulation 1223/2009 provides indications on the information that must be contained in the PIF:
- Product Description;
- Cosmetic Product Safety Report (part A and part B);
- Manufacturing method and declaration of conformity with GMP;
- Evidence of the effect attributed to the product;
- Data relating to animal testing.
Of these, the most important part of the PIF is certainly the Cosmetic Product Safety Report (CPSR), which is composed of two parts: Part A, relating to information on the safety of cosmetic products and Part B, relating to the safety assessment of cosmetic products.
The purpose of Part A is to collect the necessary data to clearly identify and quantify, based on identified hazards, the risks that a cosmetic product may pose for human health. The dangers can originate, for instance, from raw materials, the manufacturing process, packaging, conditions of use of the product, microbiology, the amounts used, the toxicological profile of the substances, etc. If the data are inadequate to make a proper assessment, the safety assessor may request additional studies to be conducted.
Part B reports the conclusions on the safety of the product. In his reasoning the safety assessor must take into account all identified hazards and expected conditions of exposure to the product.
Some European guidelines are available, but there is no standard form for the preparation of the PIF.
We would like to reiterate that the PIF is not a mere-checklist of technical documents or data to be kept but should be a reasoned and scientifically justified report, that takes into account every aspect of the finished product. Each cosmetic product represents a specific case to be examined in the complexity of its multiple facets.
Who should conduct the Safety Assessment?
The specific figure who deals with the safety assessment is the safety assessor, appointed by the responsible person in order to verify the conformity of a cosmetic product with regulation (EC) 1223/2009 and to guarantee the protection of the end user’s health. The safety assessor must be an expert person in possession of diplomas or other documents certifying formal qualifications obtained following the completion of theoretical and practical university courses in the pharmaceutical, toxicological, medical or similar disciplines, and consolidated and specific experience in the field of cosmetics.
The role of the safety assessor extends beyond the pre-market phase and continues even after the cosmetic product is placed on the market. In fact, if changes to the formula or packaging are conducted while on the market, the responsible person is required to communicate these changes to the safety assessor, who will take care of updating the documentation and safety assessment accordingly. Similarly, in the event of any adverse effects, the responsible person must promptly communicate such occurrences to the safety assessor.
How is the cosmetic safety assessment performed?
As previously depicted, the safety assessment is a complex process. It involves expert knowledge and understanding of the composition of the product, the chemical and physical properties of its ingredients, the manufacturing processes, intended use and application method of the product.
In particular, the factors to be carefully considered on a case-by-case basis when evaluating the safety of cosmetics are:
- Safety of ingredients and raw materials: this passage is done by taking into consideration toxicity studies found in the open literature, which must be adequate and reliable. After having identified the possible dangers of the ingredients, a dose-response assessment is made and a PoD (Point of Departure) usually historical NO(A)EL (no observed (adverse) effect Level) or BMDL (benchmark dose level)), identified in the bibliographic research are selected.
- Exposure assessment: the second step is the exposure assessment also called Systemic Exposure Dose (SED), an important parameter for calculating the Margin of Safety (MoS) of ingredients. The SED is the amount of a cosmetic ingredient expected to be absorbed and enter the bloodstream, thus becoming systemically available, per kg of body weight per day. However, since most cosmetic products are applied topically, systemic availability is highly dependent on skin absorption of the compound.
- Calculation of the margin of safety (MoS): the last step in evaluating the safety of a cosmetic ingredient is the calculation of the margin of safety (MoS), i.e. the ratio between a PoD and an exposure estimate (SED). A product can be considered safe when the safety margin is ≥ 100.
- Safety of the finished product: the specific requirements for conducting safety tests depend on the nature of the cosmetic product and national regulations. Typically, these tests are performed in vitro or can be conducted clinically, and the aim of the PIF is to evaluate such tests and, if needed, recommend the execution of additional testing.
What to do if a NOAEL cannot be identified?
If the NO(A)EL is not available, to calculate the MoS, a lowest dose at which an adverse effect is observed (LOAEL) by applying an additional correction factor of 3 as suggest by SCCS.
If toxicological data are not available in the literature, read-across methods are used to complete the evaluation of the ingredient under examination. Read-across is one of the most commonly used alternative approaches and this approach makes use of relevant information relating to analogous, structurally similar and well-characterised substances.
When using the read-across approach it is advisable to divide the NOAEL by an additional uncertainty factor.
In specific cases, the Threshold of Toxicological Concern (TTC) could also be used as a PoD, although not desirable.
Stakeholders may also wonder if the LD50 could also be used as the PoD. According to our opinion this is not an advisable path, as LD50 is not representative of long-lasting ingredient exposure.
What to do when an ingredient’s MoS is less than 100?
It is important to highlight that MoS should always be calculated during the early stages of product development, rather than at the end. This ensures timely adjustments can be made if an ingredient is identified as potentially posing a significant risk to end-users.
Nevertheless, there might be specific situations in which a cosmetic ingredient, though considered safe, has a safety margin of less than 100. This does not mean the ingredient must be excluded from the formula; instead, the safety evaluator, drawing on their expertise, needs to provide a justification for its inclusion in the formula. This is why Companies should always relay to experienced professionals for safety evaluations!
Should safety tests always be done?
The short answer is: NO! A manufacturing company is not obliged to carry out tests on cosmetics, as they are optional.
However, the need to carry out safety tests depends ultimately on a case-by-case basis, according to the characteristics of the raw materials used, the assessment of the evaluator and the need to support the safety claims.
How can we help you?
At ToxHub, we pride ourselves on delivering expertise in toxicology, regulatory strategy, and safety assessment for the pharmaceutical, cosmetic, and medical device industries. Elevate your product compliance journey with our dedicated team of professionals, committed to ensuring the highest standards of safety and regulatory adherence! Don’t hesitate to contact us for any inquiry.
Article Issued by Maria Labianca