Salvaging formulas in the product development cycle.

The tests that prototype formulas fail most frequently in the developmental cycle are safety tests. Why did my formula fail safety testing? is the most difficult question the toxicologist has to answer for the formulator.

The Formulator's Questions

Was the test too difficult? Were the right tests done? Did the contract laboratory do the test correctly'? What specific ingredient in the formula caused the problem? All these questions, and more, are asked by the formulator--and often by management.

The Tests

It is natural for the formulator to question whether or not the tests were too difficult, or if the right tests were even done. Corporate safety testing programs generally include preclinical tests or analyses which precede clinical tests. The preclinical tests can be in vitro tests (alternatives to animal tests), in vivo tests (animal eye and skin tests), or toxicological analyses of the formula. All are used to make a decision of whether to proceed or not to proceed to clinical testing.

Failure of a formula during in vitro preclinical testing does not necessarily preclude proceeding to clinical testing, since these tests are generally used only as screening tests.

And in vitro/in vivo test result correlations do not always help when deciding whether or not to conduct clinical testing. On the other hand, in vivo clinical tests are fairly predictive of the irritation or sensitization potential of a product.

Clinical testing typically includes human patch testing and human-use testing. Table I lists the possible reactions that can result from patch testing and use testing. The irritation, sensitization and acnegenic potential of a product can be determined by patch and use tests, which are properly conducted and interpreted.

 
Table I. Potential adverse reactions 
Irritation 
  subjective: stinging, burning, itching, tingling and tearing 
  objective: erythema, edema, pain and heat 
Sensitization 
  erythema, edema, pain and heat 
Phototoxicity 
  light-induced irritation 
Photoallergenicity 
  light-induced sensitization 
Acnegenicity/comedogenicity 
  acne breakouts, whiteheads, blackheads and pimples 
Urticaria 
  wheals and papules with itching 
Nuisance coughing 
  generally occurs only with bath products 

While possible, the failure of a product is rarely due to the type of test used in a corporate safe testing program. More …