The Mysteries of R&D, Part II: Why Do They Always Say “Not Ready Yet”?

At your company’s weekly development status meeting with R&D, it’s communicated that the new lotion has been stabilized and there are a dozen samples for testing. All the consumer testing panelists loved it, the formula has been approved and the team is ready to go into production. But wait, the R&D representative says “It’s not ready yet. We have more to do in the laboratory.”

This can be a cause for concern and frustration for both product development and marketing groups. This article will bring some insight into what goes on behind those closed laboratory doors and the cause for the “not ready yet” moments—notably label requirements and a variety of testing possibilities/necessities that should be evaluated and conducted before full production begins.

Drug vs. Cosmetic

Part of the testing program that R&D will be involved with will be determined by whether the product is classified as a cosmetic or a drug. The U.S. Food and Drug Administration (FDA) classifies a drug as an “article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.” On the other hand, a cosmetic is described as an “article intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body … for cleansing, beautifying, promoting attractiveness, or altering the appearance.”

Thus drug is defined as having an effect, while cosmetics are classified as beautifying. In the world of personal care products, an antiperspirant is a drug (has an effect on the body-reduced perspiration) while a deodorant is a cosmetic—beautifying (reducing odor) rather than an effect on the body. A shampoo is a cosmetic while an anti-dandruff shampoo is a drug (has an effect on the body). Those items that are FDA-classified as drugs but do not require a prescription are called over-the-counter (OTC ) drugs. OTC categories that impact personal care products include anti-acne, antiperspirant, antibacterial, anti-fungal, anti-dandruff, diaper rash, skin protectant and sunscreen, among others. Interestingly, the FDA does not recognize “cosmeceuticals,” which straddle both definitions. [Per the FDA website: “A product can be a drug, a cosmetic, or a combination of both, but the term ‘cosmeceutical’ has no meaning under the law.”]

Difference in Ingredient Lists—Cosmetic vs. Drug

A cosmetic must have an ingredient list that has the accepted ingredient names listed in decreasing quantitative order. Those items at 1% formula concentration or below may be placed in random order. To retail in the EU, if certain allergens are present above a specified amount, they must be listed. [Please read the Chemical Reaction column on Page 58 for further information.] The term “Fragrance/Parfum” is used and placed in the proper descending order of predominance. The composition of the fragrance need not be disclosed. A drug, on the other hand, has to have the active ingredient and percentage in the formula listed separately from the inactives. These are included in a required “Drug Facts” framed box which also contains “Warnings,” Directions for Use” and other required information.

Testing Programs

Stability for Cosmetics: This test is a predictive assessment of product shelf life. While the actual program conditions vary from company to company, a brief, general description here will be sufficient.

Samples are placed at one or two elevated temperatures, usually 45°C and 37°C, for a period of up to three months to provide for an accelerated assessment of shelf life. Evaluation at these temperatures, when compared to a sample at room temperature, will determine how the product will behave during aging. There should be little or no change during storage at the highest temperature for one month. The lower temperature samples can be observed for a longer period (three months).

Samples are also placed through three freeze-thaw cycles, where the sample is frozen for 24 hours and allowed to return to room temperature for 24 hours. This procedure is repeated two additional times. This test is usually run on emulsion systems to see if they will remain homogeneous through the three cycles.

Clear liquids (shampoos, liquid cleansers, etc.), in addition to the this testing, are evaluated at refrigeration temperature to see if they remain clear.

Samples are also exposed to light to see if there is fading or a color change. Exposure to natural light under specified conditions is usually for a period of one month. Artificial light testing can be done instrumentally in 24 hours.

Package Compatibility for Cosmetics: Essential to assure that product is not adversely affected by the package components and vice versa, these tests can be run at the same time as the stability program. The difference is that the evaluations are done in the package rather than in lab glass. Again, the testing runs from one to three months. The testing is done in such a manner as to make certain all parts of the package (pump springs, cap liner, etc.) are in contact with the product. Evaluations are done on both the product and the package to determine if there are changes in either or both.

Comparisons can be made with the product in glass to see if there are product changes due to package contact.

In addition, the product is placed in contact with the label to determine if the printing will remain unaffected.

Stability and Compatibility for OTC Drugs: For new formula OTC products, there are tests required by the FDA before going to market. It is important to remember that an OTC formula must contain only the active ingredients specified in the FDA’s monograph for the particular OTC.

Here the testing is much more extensive. The product can be marketed after three months of OTC prescribed testing (analysis of multiple batches at required temperatures, use of the commercial package, etc.). However, additional, long-term testing must be done at room/ambient temperature. In addition, chemical analysis of the active must be conducted at each testing period in addition to the physical examination. It is required that during the three-month accelerated testing program that potency of the active ingredient(s) does not fall below 90% of the labeled concentration.

Safety Testing (all products): The FDA requires that the safety of the product must be adequately substantiated. If not, the product may be considered misbranded and subject to regulatory action unless the label carries the following statement: “Warning—The safety of this product has not been determined.” A warning declaration such as that, which is required if the proper testing has not been performed, is not something that you want to have to put on your product. The safety testing will also provide assurance that the product will not produce adverse consumer reactions.

The Human Repeat Insult Patch Test (RIPT): RIPT is an industry standard for evaluation of safety. The overall time allotment is approximately six weeks to get the final report. Basically, a patch containing the product is applied to the same portion of a subject’s back every other day for nine applications. The site is observed for signs of redness (irritation response). The subject is then allowed to rest of a period of time (10–14 days) before placing a product-containing patch on another area of the subject.

This second phase measures whether there is a sensitivity reaction.

Cumulative Irritancy Testing: A 21-day or 14-day test, a patch/product is placed on a subject’s back every day for 21 days. The degree of irritation (redness, or worse) is evaluated daily. The advantage is that this is a relatively shorter test. The downside is that sensitization is not evaluated, so that a complete safety profile is not developed.

In vitro Testing: In seeking to remove the human subject from the testing scheme, various in vitro programs are being developed. At this point in time, there has been no government recognition of any as an acceptable protocol to replace the established procedures.

Clinical Testing for Claim Support: Depending on what is being said in the marketing materials and/or on the package, clinical testing may be required to support the claim. Various instrumentation is used. There are numerous techniques to evaluate these claims, and a brief description of some of the technologies are noted here.

Skin Dryness/Moisturization: Because moisture conducts an electrical current, such a current is able to quantify the amount of moisture (or lack of it) on the skin. An instrument can measure the electrical conductivity, which is translated to moisture content.

Skin Elasticity: An instrument stretches a portion of the skin then releases it, measuring its ability to return to its original state in time.

Wrinkle Reduction: A silicone mold replica is made of the area of skin under examination. The crevices in the mold can be examined microscopically, and the extent of wrinkle reduction in size and depth over time can be determined.

Skin Temperature: A measurement can determine the extent of irritation (or the reduction of it).

Trained Technical Evaluator: A trained evaluator is able to make an assessment of any changes in fine lines, skin tone, pigmentation, texture, elasticity, etc. Often, a trained evaluator is used in conjunction with the instrumentation.

Microbiological Challenge Testing (MCT): MCT is conducted to assess the product’s ability to withstand the introduction of microorganisms. During its life with the consumer, a product is exposed to contamination from many sources—airborne particles landing in an uncovered jar, fingertips immersed to pick up and apply product, etc. These sources can present numerous opportunities to contaminate the product. In anticipation of such an onslaught, an antimicrobial agent(s), a preservative, is included in a formula. The MCT will determine if the preservative is at a suitable concentration to do the job of killing any microbes to which the product is exposed. Basically, a mixture of microbes (bacteria, yeast, molds) is introduced into the product. The number of organisms is examined—usually on the day of the initial test and then days 1, 7, 14 and 28 after initial test. Examination at times within the first seven days may give a good indication as to the effectiveness of the product in staving off contamination.

Part 1 is available in the July 2010 issue.

Art Rich, PhD, is a member of the GCI magazine editorial advisory board. In addition, he is founder and chief consultant at A. Rich Development, LLC, which was founded in 2001. Rich has more than 30 years of experience in the development of marketable personal care and cosmetic formulas for such companies as Johnson & Johnson, Avon, and Bath & Body Works. He can be reached at [email protected].

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