An Algorithm to Identify Compounded Non-Sterile Products that Can Be Formulated on a Commercial Scale or Imported to Promote Safer Medication Use in Children
Abstract
:1. Introduction
2. Why Is off-Label Use of Drugs in Children Still a Problem?
- Lack of specifications required for component development by compounding pharmacies.
- No onsite testing of active ingredients and excipients for purity, potency, content and stability.
- No onsite specifications or testing of product containers and closures.
- Site-to-site variations in compounding procedures, equipment, and the degree of product handling/manipulation.
- Lack of environmental control, which might lead to unintentional contamination and generation of degradation products due to inconsistent exposure to light, temperature and processing controls.
- Lack of testing of finished products for purity, potency, content or stability.
- Stability data for establishing expiry dates of compounded products are derived from published data, where preparation methods likely vary from local methods, or are simply default expiry periods defined by regional pharmacy regulations and “best practices”.
- Published preparation methods provide only a portion of the information needed to consistently prepare a stable potent final product.
- Limited options available to mask bad-tasting active ingredients.
- The dose administration technologies used such as droppers, syringes, scoops, spoons, etc., vary between sites and between prescription fills.
- Weak regulatory oversight.
3. Development of the Algorithm for a Tiered Selection Model for Candidate APIs
3.1. Clinical and Market Considerations
- (1)
- Listed on BPCA priority document (clinical need—broad base);
- (2)
- Available in an injection (API is stable in solution for at least 18–24 months);
- (3)
- Not a federally controlled substance in Canada or the US (minimal paperwork for chain of custody);
- (4)
- Potential applicability for oral adult market (for adult patients that cannot swallow tablets or capsules);
- (5)
- Established indication for any age group in the official labeling of the API (immediate marketability through accelerated ANDA mechanism) and
- (6)
- Off-patent in both Canada and the US, and available in a pharmaceutical grade powder from a reputable supplier.
- The first tier included API molecules that met at least five of the six criteria;
- The second tier fulfilled four criteria;
- The third tier included API molecules not listed by name in the BPCA list but met all others except availability in the United Kingdom; and
- The fourth tier included those available in the UK that could be imported readily for pharmacokinetic (PK), pharmacodynamics (PD), and/or pharmacogenomics (PG) studies in children.
Generic Name | BCPA Listed? | Injection? | Non-Scheduled? | Oral Adult Market? | Established Adult Indication? | Off Patent? | Dose Form in UK? |
---|---|---|---|---|---|---|---|
Baclofen | 1 | 1 | 1 | 1 | 1 | 1 | Yes a |
Warfarin | 1 | 1 | 1 | 1 | 1 | 1 | Yes b |
Sildenafil | 1 | 1 | 1 | 1 | 1 | 1 | Yes c |
l-thyroxine | 1 | 1-lyo | 1 | 1 | 1 | 1 | Yes d |
3.2. Scientific and Production Considerations—Applying BCS and HME
API Generic Name | BCS Class | Reference |
---|---|---|
Metoprolol | II | [15] |
Clopidogrel | II | [16] |
Lisinopril | III | [16] |
Amlodipine | I | [17] |
Ursodiol | Uncl. | n.d. |
Bosentan | Uncl. | n.d. |
Pantoprazole | Uncl. | n.d. |
Acetazolamide | IV | [17] |
Spironoloactone | II/IV | [16] |
Valaciclovir | I/III | [17] |
Captopril | III | [18] |
Nifedipine | II | [16] |
Baclofen | Uncl. | n.d. |
Warfarin | I | [16] |
Sildenafil | I | [15] |
l-thyroxine | III | [16] |
4. Conclusions
Author Contributions
Conflicts of Interest
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Bhatt-Mehta, V.; MacArthur, R.B.; Löbenberg, R.; Cies, J.J.; Cernak, I.; II, R.H.P. An Algorithm to Identify Compounded Non-Sterile Products that Can Be Formulated on a Commercial Scale or Imported to Promote Safer Medication Use in Children. Pharmacy 2015, 3, 284-294. https://doi.org/10.3390/pharmacy3040284
Bhatt-Mehta V, MacArthur RB, Löbenberg R, Cies JJ, Cernak I, II RHP. An Algorithm to Identify Compounded Non-Sterile Products that Can Be Formulated on a Commercial Scale or Imported to Promote Safer Medication Use in Children. Pharmacy. 2015; 3(4):284-294. https://doi.org/10.3390/pharmacy3040284
Chicago/Turabian StyleBhatt-Mehta, Varsha, Robert B. MacArthur, Raimar Löbenberg, Jeffrey J. Cies, Ibolja Cernak, and Richard H. Parrish II. 2015. "An Algorithm to Identify Compounded Non-Sterile Products that Can Be Formulated on a Commercial Scale or Imported to Promote Safer Medication Use in Children" Pharmacy 3, no. 4: 284-294. https://doi.org/10.3390/pharmacy3040284