Reconstitution practice and delivered dose
What is the effect of reconstitution practice on the dose actually delivered from a lyophilised research peptide?
§1Abstract
§1.1Review question
What is the effect of reconstitution practice on the dose actually delivered from a lyophilised research peptide?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Lyophilised peptides reconstituted outside a pharmacy setting. |
| Intervention | Diluent choice, diluent volume, syringe graduation and storage after reconstitution. |
| Comparator | A reconstitution performed to the manufacturer’s instruction with a validated in-use period. |
| Outcomes | Delivered peptide mass; measurement error attributable to syringe graduation; loss to container surfaces; degradation over the in-use period. |
§1.3Method in brief
A review of analytical and quality evidence for a compound or class as supplied, rather than of clinical effect. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 12 January 2024 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1,2]
§1.4Conclusion
Moderate certainty evidence, principally analytical rather than clinical, indicates that three distinct errors compound in ordinary reconstitution practice: the labelled mass overstates peptide content where counter-ion and water are unquantified; adsorption to container surfaces removes a measurable fraction at low concentration in the absence of a surfactant; and graduation error on an insulin syringe becomes a large relative error below approximately four units. The Institute publishes calculators for the first and third of these and states that it can quantify neither the second nor the degradation term without compound-specific stability data.
The conclusion rests on 24 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Reconstitution practice and delivered dose received 9 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
- Wang W, Nema S, Teagarden D. Protein aggregation — pathways and influencing factors. International Journal of Pharmaceutics 2010;390(2):89–99. doi:10.1016/j.ijpharm.2010.02.025 · PMID 20188795
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.